Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.
The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Simultaneous resistance to several structurally and functionally distinct drugs.
The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).
The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).
The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).
The ability of fungi to resist or to become tolerant to chemotherapeutic agents, antifungal agents, or antibiotics. This resistance may be acquired through gene mutation.
Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Substances that reduce the growth or reproduction of BACTERIA.
The capacity of an organism to defend itself against pathological processes or the agents of those processes. This most often involves innate immunity whereby the organism responds to pathogens in a generic way. The term disease resistance is used most frequently when referring to plants.
The ability of viruses to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutation.
A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).
The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.
Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.
Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS.
Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)
Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene.
A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the p-glycoprotein family of proteins.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process.
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.
A class of plasmids that transfer antibiotic resistance from one bacterium to another by conjugation.
A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.
A cell line derived from cultured tumor cells.
Genes for MEMBRANE TRANSPORT PROTEINS that confer resistance to toxic compounds. Several superfamilies of these multidrug export proteins are known and found in both prokaryotes and eukaryotes.
Nonsusceptibility of bacteria to the action of TETRACYCLINE which inhibits aminoacyl-tRNA binding to the 30S ribosomal subunit during protein synthesis.
The ability of fungi to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutations.
Nonsusceptibility of an organism to the action of penicillins.
An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.
Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.
Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.
The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
Proteins found in any species of bacterium.
Diseases of plants.
Tests that demonstrate the relative effectiveness of chemotherapeutic agents against specific parasites.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)
A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.
A parasexual process in BACTERIA; ALGAE; FUNGI; and ciliate EUKARYOTA for achieving exchange of chromosome material during fusion of two cells. In bacteria, this is a uni-directional transfer of genetic material; in protozoa it is a bi-directional exchange. In algae and fungi, it is a form of sexual reproduction, with the union of male and female gametes.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.
Nonsusceptibility of bacteria to the action of the beta-lactam antibiotics. Mechanisms responsible for beta-lactam resistance may be degradation of antibiotics by BETA-LACTAMASES, failure of antibiotics to penetrate, or low-affinity binding of antibiotics to targets.
Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.
A type of strength-building exercise program that requires the body muscle to exert a force against some form of resistance, such as weight, stretch bands, water, or immovable objects. Resistance exercise is a combination of static and dynamic contractions involving shortening and lengthening of skeletal muscles.
A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Nonsusceptibility of bacteria to the action of CHLORAMPHENICOL, a potent inhibitor of protein synthesis in the 50S ribosomal subunit where amino acids are added to nascent bacterial polypeptides.
Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
The functional hereditary units of BACTERIA.
The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.
A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections.
Nonsusceptibility of a microbe to the action of ampicillin, a penicillin derivative that interferes with cell wall synthesis.
Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.
Elements of limited time intervals, contributing to particular results or situations.
An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.
Proteins encoded by the POL GENE of the HUMAN IMMUNODEFICIENCY VIRUS.
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.
An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins.
Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
A subfamily of transmembrane proteins from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS that are closely related in sequence to P-GLYCOPROTEIN. When overexpressed, they function as ATP-dependent efflux pumps able to extrude lipophilic drugs, especially ANTINEOPLASTIC AGENTS, from cells causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although P-Glycoproteins share functional similarities to MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS they are two distinct subclasses of ATP-BINDING CASSETTE TRANSPORTERS, and have little sequence homology.
Five membered rings containing a NITROGEN atom.
Agents used to treat RETROVIRIDAE INFECTIONS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
An enzyme that catalyzes the formation of dihydropteroate from p-aminobenzoic acid and dihydropteridine-hydroxymethyl-pyrophosphate. EC 2.5.1.15.
An antibiotic first isolated from cultures of Streptomyces venequelae in 1947 but now produced synthetically. It has a relatively simple structure and was the first broad-spectrum antibiotic to be discovered. It acts by interfering with bacterial protein synthesis and is mainly bacteriostatic. (From Martindale, The Extra Pharmacopoeia, 29th ed, p106)
Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.
The relationships of groups of organisms as reflected by their genetic makeup.
Proteins found in any species of protozoan.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis).
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Non-susceptibility of a microbe to the action of METHICILLIN, a semi-synthetic penicillin derivative.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
A calcium channel blocker that is a class IV anti-arrhythmia agent.
A group of SESQUITERPENES and their analogs that contain a peroxide group (PEROXIDES) within an oxepin ring (OXEPINS).
Established cell cultures that have the potential to propagate indefinitely.
Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.
The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.
Large cytoplasmic ribonucleoprotein particles that have an eight-fold symmetry with a central pore and petal-like structure giving the appearance of an octagonal dome. (The Dictionary of Cell Biology, Lackie and Dow, 2nd ed.)
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
MYCOBACTERIUM infections of the lung.
Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM.
Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins.
Vertical transmission of hereditary characters by DNA from cytoplasmic organelles such as MITOCHONDRIA; CHLOROPLASTS; and PLASTIDS, or from PLASMIDS or viral episomal DNA.
Nonsusceptibility of bacteria to the action of VANCOMYCIN, an inhibitor of cell wall synthesis.
Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.
A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.
Therapy with two or more separate preparations given for a combined effect.
The action of a drug in promoting or enhancing the effectiveness of another drug.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
The quantity of measurable virus in a body fluid. Change in viral load, measured in plasma, is sometimes used as a SURROGATE MARKER in disease progression.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
Genotypic differences observed among individuals in a population.
Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.
Non-susceptibility of an organism to the action of the cephalosporins.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.
A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.
Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.
Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.
A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV INFECTIONS and AIDS.
Tuberculosis resistant to ISONIAZID and RIFAMPIN and at least three of the six main classes of second-line drugs (AMINOGLYCOSIDES; polypeptide agents; FLUOROQUINOLONES; THIOAMIDES; CYCLOSERINE; and PARA-AMINOSALICYLIC ACID) as defined by the CDC.
Nonsusceptibility of bacteria to the antibiotic KANAMYCIN, which can bind to their 70S ribosomes and cause misreading of messenger RNA.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Diminished or failed response of PLANTS to HERBICIDES.
Substances that are destructive to protozoans.
Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.
Agents that inhibit PROTEIN KINASES.
Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033)
Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
A broad-spectrum antimicrobial carboxyfluoroquinoline.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
An anthracenedione-derived antineoplastic agent.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A group of compounds that contain the structure SO2NH2.
A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Carbon-containing phosphonic acid compounds. Included under this heading are compounds that have carbon bound to either OXYGEN atom or the PHOSPHOROUS atom of the (P=O)O2 structure.
Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.
Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.
DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.
DNA sequences that form the coding region for retroviral enzymes including reverse transcriptase, protease, and endonuclease/integrase. "pol" is short for polymerase, the enzyme class of reverse transcriptase.
Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.
An antitumor alkaloid isolated from VINCA ROSEA. (Merck, 11th ed.)
A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Tumors or cancer of the human BREAST.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Transport proteins that carry specific substances in the blood or across cell membranes.
Deoxyribonucleic acid that makes up the genetic material of protozoa.
A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are PLASMODIUM FALCIPARUM; PLASMODIUM MALARIAE; PLASMODIUM OVALE, and PLASMODIUM VIVAX. Species causing infection in vertebrates other than man include: PLASMODIUM BERGHEI; PLASMODIUM CHABAUDI; P. vinckei, and PLASMODIUM YOELII in rodents; P. brasilianum, PLASMODIUM CYNOMOLGI; and PLASMODIUM KNOWLESI in monkeys; and PLASMODIUM GALLINACEUM in chickens.
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.
Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.
Any method used for determining the location of and relative distances between genes on a chromosome.
A phospholipid-interacting antimalarial drug (ANTIMALARIALS). It is very effective against PLASMODIUM FALCIPARUM with very few side effects.
A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.
Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.
DNA elements that include the component genes and insertion site for a site-specific recombination system that enables them to capture mobile gene cassettes.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Ribonucleic acid that makes up the genetic material of viruses.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Using MOLECULAR BIOLOGY techniques, such as DNA SEQUENCE ANALYSIS; PULSED-FIELD GEL ELECTROPHORESIS; and DNA FINGERPRINTING, to identify, classify, and compare organisms and their subtypes.
A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.
A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with well-defined distribution patterns in relation to time or place or both.
A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.
This line KB is now known to be a subline of the ubiquitous KERATIN-forming tumor cell line HeLa. It was originally thought to be derived from an epidermal carcinoma of the mouth, but was subsequently found, based on isoenzyme analysis, HeLa marker chromosomes, and DNA fingerprinting, to have been established via contamination by HELA CELLS. The cells are positive for keratin by immunoperoxidase staining. KB cells have been reported to contain human papillomavirus18 (HPV-18) sequences.
A fluorescent probe with low toxicity which is a potent substrate for P-glycoprotein and the bacterial multidrug efflux transporter. It is used to assess mitochondrial bioenergetics in living cells and to measure the efflux activity of P-glycoprotein in both normal and malignant cells. (Leukemia 1997;11(7):1124-30)
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility.
3,6-Diamino-10-methylacridinium chloride mixt. with 3,6-acridinediamine. Fluorescent dye used as a local antiseptic and also as a biological stain. It intercalates into nucleic acids thereby inhibiting bacterial and viral replication.
One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.
A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are found on the skin and mucous membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.
Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.
Glucose in blood.

Foscarnet therapy for ganciclovir-resistant cytomegalovirus retinitis after stem cell transplantation: effective monitoring of CMV infection by quantitative analysis of CMV mRNA. (1/2958)

We report three pediatric patients with ganciclovir-resistant cytomegalovirus (CMV) retinitis who were successfully treated with foscarnet. The patients were recipients of hematopoietic stem cell transplantation (SCT) from HLA-mismatched donors. Because these patients had developed or experienced progressive CMV retinitis during ganciclovir therapy, they received foscarnet therapy at 60 mg/kg every 8 h. Their retinitis resolved promptly after initiating foscarnet therapy, suggesting foscarnet's effectiveness in treating ganciclovir-resistant CMV infection. The amount of CMV mRNA was quantitatively measured using an NASBA technique, which amplified the beta2.7 transcripts specific for CMV replication. This technique was useful for monitoring disease activity in a more rapid and sensitive manner than the PCR assay for CMV DNA.  (+info)

Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance. (2/2958)

We describe a case of CMV ventriculoencephalitis in a severely immunocompromised bone marrow transplant recipient who was receiving combination therapy with ganciclovir and foscarnet for treatment of viremia and retinitis. Analysis of sequential viral isolates recovered from the patient's cerebrospinal fluid suggested that disease developed because of the presence of viral resistance and, possibly, low tissue penetration of antiviral agents.  (+info)

Antiretroviral resistance mutations among pregnant human immunodeficiency virus type 1-infected women and their newborns in the United States: vertical transmission and clades. (3/2958)

To assess the impact of antiretroviral resistance on perinatal transmission prevention efforts, human immunodeficiency virus type 1 (HIV-1) genotypic resistance testing was done for 220 HIV-1-infected, zidovudine (AZT)-exposed pregnant women and 24 of their infected infants. The women were prospectively enrolled in 4 US cities in 1991-1997. Phylogenetic and sequencing analyses revealed 5 women with non-clade B infections traced to western African origins. AZT-associated mutations were detected in 17.3% of pregnant women, whereas genotypic resistance to nonnucleoside reverse-transcriptase inhibitors and protease inhibitors was infrequent. No significant association was detected between perinatal transmission and the presence of either AZT or nucleoside reverse-transcriptase inhibitor resistance-associated mutations. AZT resistance mutations were detected in 2 (8.3%) neonatal samples, but the mutation pattern was not identical to the mother's. Although no effect of viral resistance on mother-infant transmission was demonstrated, the advent of more-potent drug classes and the potential for the rapid emergence of resistance warrant prospective surveillance.  (+info)

Characterization of the DNA polymerase gene of varicella-zoster viruses resistant to acyclovir. (4/2958)

The nucleotide changes of the DNA polymerase gene and the susceptibility of acyclovir (ACV)-resistant varicella-zoster virus (VZV) mutants to anti-herpetic drugs were determined and compared to those of herpes simplex virus type 1 (HSV-1) mutants. The seven ACV-resistant VZV mutants were classified into three groups, N(779)S, G(805)C and V(855)M, according to the sequences of their DNA polymerase genes. The amino acid substitutions N(779)S and G(805)C were identical in position to the N(815)S and G(814)C mutations in the HSV-1 DNA polymerase mutants, respectively, and the V(855)M amino acid substitution was similar to the HSV-1 V(892)M mutation. All three groups of VZV mutants were susceptible to ACV, phosphonoacetic acid, vidarabine and aphidicolin, at levels similar to those seen with the respective HSV-1 mutants, except for subtle differences that were due possibly to the non-conserved regions in their sequences. Although both the HSV-1 and the VZV DNA polymerase genes show 53% sequence similarity, both viruses essentially show a similar biochemical behaviour.  (+info)

Selection of the same mutation in the U69 protein kinase gene of human herpesvirus-6 after prolonged exposure to ganciclovir in vitro and in vivo. (5/2958)

After serial passage in the presence of increasing concentrations of ganciclovir (GCV) in vitro, a human herpesvirus-6 (HHV-6) mutant exhibiting a decreased sensitivity to the drug was isolated. Analysis of drug susceptibility showed that the IC(50) of this mutant was 24-, 52- and 3-fold higher than that of the wild-type (wt) IC(50) in the case of GCV, cidofovir and foscarnet, respectively. Genotypic analysis showed two single nucleotide changes as compared to the wild-type: an A-->G substitution of the U69 protein kinase (PK) gene resulted in an M(318)V amino acid substitution and the other change, located in the C-terminal part of the U38 gene, resulted in an A(961)V amino acid substitution within the DNA polymerase. The M(318)V change was located within the consensus sequence DISPMN of the putative catalytic domain VI of the PK. This change was homologous to the M(460)V and M(460)I changes that had been reported previously within the consensus sequence DITPMN of the human cytomegalovirus (HCMV) UL97 PK and associated with the resistance of HCMV to GCV. The M(318)V change was also detected by PCR in HHV-6-infected PBMCs from an AIDS patient who had been treated with GCV for a long period of time and exhibited a clinically GCV-resistant HCMV infection. These findings provide strong circumstantial evidence that the M(318)V change of the PK gene is associated with resistance to GCV and raise the question of cross resistance to this drug among different betaherpesviruses.  (+info)

The emergence of different resistance mechanisms toward nucleoside inhibitors is explained by the properties of the wild type HIV-1 reverse transcriptase. (6/2958)

Nucleoside reverse transcriptase inhibitors (NRTIs) represent one of the main drug families used against AIDS. Once incorporated in DNA, they act as chain terminators, due to the lack of a 3'-hydroxyl group. As for the other anti-human immunodeficiency virus type 1 drugs, their efficiency is limited by the emergence of resistant viral strains. Unexpectedly, previous studies indicated that resistance toward NRTIs is achieved via two distinct and generally exclusive mechanisms. Resistance mutations either decrease the efficiency of NRTIs incorporation or increase their excision from the extended primer. To understand the emergence of different resistance mechanisms toward a single inhibitor class, we compared the incorporation and the pyrophosphorolysis of several NRTIs using wild type reverse transcriptase (WT RT). We found that the efficiency of discrimination or excision by pyrophosphorolysis in the presence of nucleotides of a given NRTI is a key determinant in the emergence of one or the other resistance pathway. Indeed, our results suggest that the pathway by which RT become resistant toward a given NRTI can be predicted by studying the inhibition of WT RT, because the resistance mutations do not confer new properties to the mutant enzyme, but rather exacerbate pre-existing properties of the WT enzyme. They also help to understand the low cross-resistance toward d4T observed with the 3'-azido-3'-deoxythymidine (AZT or zidovudine)-resistant RT.  (+info)

Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naive persons. (7/2958)

Transmission of HIV-1 with reduced susceptibility to antiretroviral drugs raises public health concerns. Through surveillance of drug-resistant HIV-1 in 603 treatment-naive, recently diagnosed HIV-1-infected persons, we identified a distinct group of viruses that have mutations at codon 215 of the reverse transcriptase (RT) gene that are different from either the wild-type (WT) T or the zidovudine (AZT)-selected T215Y/F. These mutations included 215D/C/S and were found in 20 patients (3.3%). The 215D, 215C, and 215S mutations differ from 215Y by a 1-nt change compared with 2 nt for the WT T215 and likely represent revertants of 215Y. These viruses all were found to have WT susceptibility to AZT, and all replicated efficiently as WT HIV-1(T215). However, differences in fitness among HIV-1(215D), HIV-1(215C), and HIV-1(215S) were seen when RT backgrounds were changed, demonstrating a role of the RT background in the selection of these revertants. In vitro selection with AZT showed that HIV-1(215D) and HIV-1(215C) acquired 215Y more rapidly than did WT HIV-1(T215), likely reflecting the need for only 1-nt change to evolve to 215Y. Our study demonstrates that HIV-1 with unusual mutations at codon 215 replicate efficiently, have WT susceptibility, and are commonly found in treatment-naive persons. The increased ability for selecting resistance mutations defines this class of WT HIV-1 and highlights the higher potential of these viruses to compromise the efficacy of antiretroviral therapy.  (+info)

Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir. (8/2958)

BACKGROUND: Strategies for prevention of liver graft reinfection by hepatitis B virus (HBV) have been developed during recent years. Initially, passive immunoprophylaxis with high titre HBV immunoglobulin (HBIg), followed by lamivudine prophylaxis, and then the combination of lamivudine and HBIg have been employed. However, suboptimal use of the combination may be associated with failure of prophylaxis reflected by the emergence of HBV species with genetic changes that confer resistance to lamivudine and HBIg. Reinfection of the graft by HBV can be associated with rapid development of liver failure. CASE REPORT: A 43 year old HBV infected man received lamivudine before transplantation, and lamivudine and HBIg after transplantation. Despite prophylaxis, graft reinfection and severe hepatitis were observed. The observed serological evolution and genetic sequencing of the emergent HBV species suggested selection of lamivudine resistant and surface antigen escape mutants consecutively. Adefovir treatment began after the development of graft failure. OUTCOME: A rapid exponential decline in serum HBV titre was observed. Liver function tests normalised and signs of liver failure resolved. CONCLUSION: The use of HBIg and lamivudine permits prevention of graft reinfection by HBV for the majority of patients. Adefovir, a potent inhibitor of lamivudine resistant HBV, should be used when failure of prophylaxis is associated with graft hepatitis.  (+info)

The 2009 report for the UK HIV Drug Resistance Database is now available to download.. The UK HIV Drug Resistance Database was established in 2001 as a national repository for resistance tests, giving rise to an important scientific resource. It has been highly successful, capturing 90-95% of all tests conducted.. The report outlines the achievements of the Database in the previous year including highlights of the various analyses that have been carried out.. If you would like to order a hard copy of the report, please send your request via email.. For more information, please visit the UK HIV Drug Resistance Database website.. ...
Castro H, Dunn DT, Cane P A, Asboe D, Cambiano V, Phillips AN, Pillay D, UK HIV Drug Resistance Database. 2012. Persistence of transmitted HIV drug resistance mutations. International Workshop on HIV & Hepatitis Virus Resistance and Curative Strategies, 5-9 June 2012. Antiviral Therapy 17 Suppl 1:A167. ...
Geretti AM, White E, Beloukas A, Orkin C, Tostevin A, Tilston P, Chadwick D, Leen C, Sabin CA, Dunn DT, UK HIV Drug Resistance Database and UK Collaborative HIV Cohort ...
Abbott RealTime HBV Assay Is More Sensitive in Detection of Low Viral Load and Little Impacted by Drug Resistant Mutation in Chronic Hepatitis B Patients under Nucleotside Analogues Therapy. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
If HIV-1 RNA titer (HIVDQ / HIV-1 RNA Detection and Quantification, Plasma) is 500 copies/mL or higher, then HIV-1 genotypic drug resistance mutations (HIVPR / HIV-1 Genotypic Protease and Reverse Transcriptase Inhibitor Drug Resistance, Plasma) will be performed at an additional charge.. See HIV Treatment Monitoring Algorithm in Special Instructions.. ...
We investigated the evolution of HIV reverse transcriptase (RT)- and protease-associated antiretroviral (ARV) drug resistance mutations during the time taken to perform genotypic drug resistance testing. Thirty treatment-experienced patients who were adherent to therapy and who underwent genotypic drug resistance testing provided blood samples at randomization and when reviewing the test results (baseline). Patients remained on their existing therapy between randomization and baseline. The predominant HIV strains in 10 patients (33%) either lost and/or gained primary RT inhibitor (RTI) or protease inhibitor (PI) associated resistance mutations during the testing period. Of the 9 patients with RT mutations, 2 lost, 5 gained, and 2 both lost and gained RTI resistance mutations. One patient gained a significant PI-associated resistance mutation on an existing PI-resistant background. The evolution that occurred in the RT may have altered the effectiveness of subsequent ARV therapy in some patients ...
The Stanford University HIV Drug Resistance Database is the most comprehensive web site devoted to HIV drug resistance, providing a very popular and regularly updated genotypic resistance interpretation algorithm (HIVdb). The system accepts user-submitted protease (PR) and reverse transcriptase (RT) sequences and returns inferred levels of resistance to 19 PR and RT inhibitors. Its purpose is educational and as such it provides extensive comments and a highly transparent scoring system that is hyperlinked to data in the HIV Drug Resistance Database. Other relevant features include HIValg, a program to compare the most commonly used genotypic resistance algorithms and an expanding array of statistics and query pages on HIV drug resistance. ...
BC-CfE - Automating HIV drug resistance genotyping with RECall, a freely accessible sequence analysis tool. - Genotypic HIV drug resistance testing is routinely used to guide clinical decisions.
BACKGROUND:Accurate quantification of the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance in patients who are receiving antiretroviral therapy (ART) is difficult, and results from previous studies vary. We attempted to assess the prevalence and dynamics of resistance in a highly representative patient cohort from Switzerland. METHODS:On the basis of genotypic resistance test results and clinical data, we grouped patients according to their risk of harboring resistant viruses. Estimates of resistance prevalence were calculated on the basis of either the proportion of individuals with a virologic failure or confirmed drug resistance (lower estimate) or the frequency-weighted average of risk group-specific probabilities for the presence of drug resistance mutations (upper estimate). RESULTS:Lower and upper estimates of drug resistance prevalence in 8064 ART-exposed patients were 50% and 57% in 1999 and 37% and 45% in 2007, respectively. This decrease was driven by 2 ...
2. With a simple alteration of denaturation temperature in the thermal cycle, COLD-PCR could detect drug resistance mutations that existed at a level of 5-10% within a mixed pool, compared with a level of ≥25% for conventional PCR ...
Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates. pts= ...
Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates. pts= ...
Para MF, Glidden DV, Coombs RW, Collier AC, Condra JH, Craig C, Bassett R, Leavitt R, Snyder S, McAuliffe V, Boucher C, AIDS Clinical Trials Group Protocol 333 Team. Baseline Human Immunodeficiency Virus Type 1 Phenotype, Genotype, and RNA Response after Switching from Long-Term Hard-Capsule Saquinavir to Indinavir or Soft-GelndashCapsule Saquinavir in AIDS Clinical Trials Group Protocol 333. J Infect Dis. 2000 Sep;182(3):733-43 ...
Seegene Inc., (KOSDAQ: 096530), a leading developer of multiplex molecular diagnostic technologies and tests, today announced that it will introduce Quantplex MTB/MDR/XDR Detection, a real time test that detects Mycobacterium tuberculosis and resistance mutations associated with multiple drug resistant (MDR) and extensively drug resistant (XDR) forms of M
UNLABELLED: The efficacy of specifically targeted anti-viral therapy for hepatitis C virus (HCV) (STAT-C), including HCV protease and polymerase inhibitors, is limited by the presence of drug-specific viral resistance mutations within the targeted proteins. Genetic diversity within these viral proteins also evolves under selective pressures provided by host human leukocyte antigen (HLA)-restricted immune responses, which may therefore influence STAT-C treatment response. Here, the prevalence of drug resistance mutations relevant to 27 developmental STAT-C drugs, and the potential for drug and immune selective pressures to intersect at sites along the HCV genome, is explored. HCV nonstructural (NS) 3 protease or NS5B polymerase sequences and HLA assignment were obtained from study populations from Australia, Switzerland, and the United Kingdom. Four hundred five treatment-naïve individuals with chronic HCV infection were considered (259 genotype 1, 146 genotype 3), of which 38.5% were coinfected with
This tool takes as input a set of Gag-Pol sequences including the gene for the viral PR and one or more of its CSs, and produces a prediction for potential secondary drug resistance mutations in the latter. The cleavage of the Gag-Pol polyprotein by the PR is essential for the infectivity of HIV virions. PI therapy can give rise to primary resistance mutations in the PR, which are often associated with a decreased activity of the enzyme. Impaired function can be partially restored by compensatory mutations in the CS, probably by providing a better substrate for the mutated proteases. Associated pairs of mutations have been detected from large sets of sequences (populations of molecules) by covariation analysis (Hoffman et al. 2003), and we have extended this approach to identify CS mutations that arise in response to primary resistance mutations in the PR. We analysed HIV-1 subtype B nucleotide sequences containing the protease region from the Los Alamos HIV Sequence Database ...
Background: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. Results: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients ...
The major limitation of drug resistance genotyping for human immunodeficiency virus remains the interpretation of the results. We evaluated the concordance in predicting therapy response between four different interpretation algorithms (Rega 6.3, HIVDB-08/04, ANRS [07/04], and VGI 8.0). Sequences were gathered through a worldwide effort to establish a database of non-B subtype sequences, and demographic and clinical information about the patients was gathered. The most concordant results were found for nonnucleoside reverse transcriptase (RT) inhibitors (93%), followed by protease inhibitors (84%) and nucleoside RT inhibitor (NRTIs) (76%). For therapy-naive patients, for nelfinavir, especially for subtypes C and G, the discordances were driven mainly by the protease (PRO) mutational pattern 82I/V + 63P + 36I/V for subtype C and 82I + 63P + 36I + 20I for subtype G. Subtype F displayed more discordances for ritonavir in untreated patients due to the combined presence of PRO 20R and 10I/V. In ...
Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS). All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR) determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models ...
It can. Say you are positive and not on treatment. Chances are your virus will not have any drug resistant mutations. If you come in contact with someone who is on meds, with detectable virus, and...
Schuurman, R., Brambilla, D., De Groot, T., Huang, D., Land, S., Bremer, J., ... Boucher, C. (2002). Underestimation of HIV Type I drug resistance mutations: Results from the ENVA-2 genotyping proficiency program. AIDS Research and Human Retroviruses, 18, 243 - 48. ...
The introduction of antiretroviral therapy (ART) has intensely reduced HIV-1 associated deaths, mother-to-child HIV-1 transmission, and adult HIV-1 rates. This is as a result of the extensive administration of homogeneous first line regimens that contain two nucleoside reverse transcriptase inhibitors commonly referred to as NRTIs as well as a nonnucleoside RT inhibitor referred to as NNRT. Unfortunately, the long-term success of ART is affected by the development of acquired drug resistance (ADR) and transmitted drug resistance (TDR).. There is an increasing popularity of acquired and transmitted HIV-1 drug resistance. This has consequently become a major obstacle to the success of antiretroviral therapy in the low and middle-income countries that have been hit hardest by the HIV-1 epidemic. To address this issue, experts recommend genotypic drug resistance testing to facilitate the choice of initial ART in areas where there is an increase in transmitted drug resistance. This will also enable ...
Purpose of review: Surveillance for transmitted HIV drug resistance is essential to assessing the longer term sustainability and durability of first-line antiretroviral therapy (ART).
CHEMICAL RESISTANCE DATA for Fittings SheetThe judging criteria of the chemical resistance data are made under the fixed circumstances. Thus, depending on how you use hoses, out product may not be used even though the chemical resistance
HIV-1 protease recognizes and cleaves more than 12 different substrates leading to viral maturation. While these substrates share no conserved motif, they are specifically selected for and cleaved by protease during viral life cycle. Drug resistant mutations evolve within the protease that compromise inhibitor binding but allow the continued recognition of all these substrates. While the substrate envelope defines a general shape for substrate recognition, successfully predicting the determinants of substrate binding specificity would provide additional insights into the mechanism of altered molecular recognition in resistant proteases. We designed a variant of HIV protease with altered specificity using positive computational design methods and validated the design using X-ray crystallography and enzyme biochemistry. The engineered variant, Pr3 (A28S/D30F/G48R), was designed to preferentially bind to one out of three of HIV proteases natural substrates; RT-RH over p2-NC and CA-p2. In kinetic ...
As discussed in What is Drug Resistance?, HIV drug resistance means a reduction in the ability of a drug -- or combination of drugs -- to block HIV ...
General Principles of Regimen Switching. The fundamental principle of regimen switching is to maintain viral suppression without jeopardizing future treatment options (AI). If a regimen switch results in virologic failure with the emergence of new resistance mutations, the patient may require more complex or expensive regimens.. The review of a patients full antiretroviral (ARV) history-including virologic responses, past ARV-associated toxicities, and cumulative resistance test results (if available)-is warranted before any treatment switch (AI). If a patient with pre-ART wild-type HIV achieves and maintains viral suppression after ART initiation, one can assume that no new resistance mutation emerged while the patient was on the suppressive regimen.. Once selected, a resistance mutation is generally archived in the HIV reservoir and is likely to re-emerge under the appropriate selective drug pressure, even if not detected in the patients most recent resistance test. If resistance data are ...
The emergence of drug resistance remains a major problem for the treatment of HIV-infected patients. However, the variety of mutational patterns that evolve in clinical practice have made the application of resistance data to clinical decision-making challenging. Despite (or because of) an abundance of drug-resistance data from disparate sources, there is only limited information available describing the patterns of drug resistance which usually appear in the clinic.
UNLABELLED: The R263K substitution in integrase has been selected in tissue culture with dolutegravir (DTG) and has been reported for several treatment-experienced individuals receiving DTG as part of salvage therapy. The R263K substitution seems to be incompatible with the presence of common resistance mutations associated with raltegravir (RAL), a different integrase strand transfer inhibitor (INSTI). T66I is a substitution that is common in individuals who have developed resistance against a different INSTI termed elvitegravir (EVG), but it is not known whether these two mutations might be compatible in the context of resistance against DTG or what impact the combination of these substitutions might have on resistance against INSTIs. E138K is a common secondary substitution observed with various primary resistance substitutions in RAL- and EVG-treated individuals. Viral infectivity, replicative capacity, and resistance against INSTIs were measured in cell-based assays. Strand transfer and 3 ...
Drug resistance testing before initiation of, or during, antiretroviral therapy (ART) is not routinely performed in resource-limited settings. High levels of viral resistance circulating within the population will have impact on treatment programs by increasing the chances of transmission of resistant strains and treatment failure. Here, we investigate Drug Resistance Mutations (DRMs) from blood samples obtained at regular intervals from patients on ART (Baseline-22 months) in Karonga District, Malawi. One hundred and forty nine reverse transcriptase (RT) consensus sequences were obtained via nested PCR and automated sequencing from blood samples collected at three-month intervals from 75 HIV-1 subtype C infected individuals in the ART programme. Fifteen individuals showed DRMs, and in ten individuals DRMs were seen from baseline samples (reported to be ART naïve). Three individuals in whom no DRMs were observed at baseline showed the emergence of DRMs during ART exposure. Four individuals who ...
The prices of reverse transcriptase (RT) inhibitors in Thailand have been reduced since December 1, 2001. It is expected that reduction in the price of these inhibitors may influence the drug resistance mutation pattern of HIV-1 among infected people. This study reports the frequency of HIV-1 genetic mutation associated with drug resistance in antiretroviral-treated patients from Thailand. Genotypic resistance testing was performed on samples collected in 2002 from 88 HIV-1 infected individuals. Automated DNA sequencing was used to genotype the HIV-1 polymerase gene isolated from patients plasma. Resistance to protease inhibitors, nucleoside and non-nucleoside reverse transcriptase inhibitors were found in 10 (12%), 42 (48%) and 19 (21%) patients, respectively. The most common drug resistance mutations in the protease gene were at codon 82 (8%), 90 (7%) and 54 (6%), whereas resistant mutations at codon 215 (45%), 67 (40%), 41 (38%) and 184 (27%) were commonly found in the RT gene. This finding
Despite the increasing use of antiretroviral treatment (ART) recent data on frequency and pattern of drug resistance mutations in Ethiopia is not available. Furthermore with increasing mobility of people HIV-1 subtypes other than the predominant subtype C may likely be introduced from the neighbouring countries. This study was aimed to determine the molecular characterization and pre-antiretroviral treatment resistance mutations among HIV-1 chronically infected ART naïve patients after the roll out of ART in Ethiopia. Viral RNA was determined in 160 baseline plasma samples. The entire PR and the first 335 codons (76%) of the RT regions of the pol gene of the HIV-1 genome (N = 160) were amplified and sequenced using an in-house assay. Genotypic drug resistance was defined as the presence of one or more resistance-related mutations as specified by the consensus mutation of Stanford University HIVDB and the International Antiviral Society (IAS) mutation lists. A predominance of HIV-1 subtype C (98.7%) was
David joined the Unit in 1998 after previous spells at London School of Hygiene and Tropical Medicine and the Institute of Child Health. In 1997 he gained a PhD on statistical issues around the vertical transmission of HIV infection.. His main current research interest is HIV drug resistance. He is the co-PI of the UK HIV Drug Resistance Database (UKHDRD), which aims to collect all resistance tests performed as part of routine clinical care in the UK and to link these to key clinical/demographic data. He has a particular interest in the epidemiology of transmitted drug resistance and UKHDRD has provided several important insights on this topic.. A more recent development is collaborating with Dr Sheena McCormack to design and implement a pragmatic randomised controlled trial to assess the effectiveness of pre-exposure prophylaxis to reduce the risk of HIV transmission among gay men in the UK. Although the biological efficacy of this intervention has been clearly established, its real-life ...
Eligible patients were ART-naïve, were ≥ 19 years old, had initiated ART between 1 January 2000 and 31 December 2012, had ≥ 15 months of follow-up, and were without transmitted HIVDR. Patients were followed for acquired HIVDR until 31 March 2014, the last contact date, or death. We built logistic regression models to assess the associations and predictive ability of individual indicators and of the EWI Score (the number of indicators for which a patient did not meet the criteria) on HIVDR acquisition (to any class of HIVDR, lamivudine (3TC)/emtricitabine (FTC), nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors (PIs)]).. RESULTS ...
Understanding the mechanisms of viral drug resistance is critical to the clinical management of individuals receiving antiviral therapy, the development of new antiviral drugs, and the surveillance of drug resistance. This chapter reviews the mechanisms of resistance to antiviral agents used to treat seven common viral infections, i.e., infections with herpes simplex virus (HSV), cytomegalovirus (CMV), varicella-zoster virus (VZV), human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), influenza A and B viruses, hepatitis B virus (HBV), and hepatitis C virus (HCV). Antiviral drug resistance is usually mediated by mutations in the molecular targets of drug therapy, and the development of drug resistance is the most compelling evidence that an antiviral drug acts by specifically inhibiting a virus rather than its cellular host. Drug-resistant viruses are identified by in vitro passage experiments with increasing concentrations of an inhibitory drug and by ex vivo analysis of virus isolates obtained
HIV drug resistance is increasing rapidly in southern and eastern Africa and Latin America and, as a result, it may soon be necessary to change the recommended first-line antiretroviral drug regimen in many countries to integrase inhibitor-based treatment, according to an analysis published in Lancet ...
Five out of 36 consecutive patients (13.89%, 95% CI = 4.67-29.5) with acute/recent HIV infection were detected to have strains carrying InSTI polymorphisms or substitutions conferring low-level resistance to raltegravir and elvitegravir. Four patients had the 157Q polymorphism and one patient had the Q95K substitution. All cases were MSM patients infected with subtype B strains. Viral loads ranged from 2.92 to 6.95 log10 copies/mL. In all cases, the mutational viral load was high. Three patients initiated dolutegravir-based regimens and became undetectable at first viral load control. There were no major viral or epidemiological differences when compared with patients without InSTI substitutions.. CONCLUSIONS ...
Few studies have investigated sequential HIV-1 mutation changes in the HIV gene in patients changing antiretroviral drugs. We analyze such data from the HIV Drug Resistance Database at Stanford University using three data mining methods: association rule analysis, logistic regression, and classifica …
Antiretroviral drugs are a very effective therapy against HIV infection. However, the high mutation rate of HIV permits the emergence of variants that can be resistant to the drug treatment. Predicting drug resistance to previously unobserved variants is therefore very important for an optimum medical treatment. In this paper, we propose the use of weighted categorical kernel functions to predict drug resistance from virus sequence data. These kernel functions are very simple to implement and are able to take into account HIV data particularities, such as allele mixtures, and to weigh the different importance of each protein residue, as it is known that not all positions contribute equally to the resistance. We analyzed 21 drugs of four classes: protease inhibitors (PI), integrase inhibitors (INI), nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI). We compared two categorical kernel functions, Overlap and Jaccard, against two well-known
Using real-time PCR to detect HIV resistance mutations present at low levels, Jeffrey Johnson and colleagues investigate prevalence and clinical implications of minority transmitted mutations.
Betancor G, Garriga C, Puertas MC, Nevot M, Anta L, Blanco JL, Pérez-Elías MJ, de Mendoza C, Martínez MA, Martinez-Picado J, Menéndez-Arias L; Resistance Platform of the Spanish AIDS Research Network (ResRIS), Iribarren JA, Caballero E, Ribera E, Llibre JM, Clotet B, Jaén A, Dalmau D, Gatel JM, Peraire J, Vidal F, Vidal C, Riera M, Córdoba J, López Aldeguer J, Galindo MJ, Gutiérrez F, Álvarez M, García F, Pérez-Romero P, Viciana P, Leal M, Palomares JC, Pineda JA, Viciana I, Santos J, Rodríguez P, Gómez Sirvent JL, Gutiérrez C, Moreno S, Pérez-Olmeda M, Alcamí J, Rodríguez C, del Romero J, Cañizares A, Pedreira J, Miralles C, Ocampo A, Morano L, Aguilera A, Garrido C, Manuzza G, Poveda E, Soriano V. Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Retrovirology. 2012 Aug 13;9:68. doi: ...
Background - Studies have shown that low-frequency resistance mutations can influence treatment outcome. However, the lack of a standardized high-throughput assay has precluded their detection in clinical settings.. Objective - To evaluate the performance of the Roche prototype 454 UDS HIV-1 drug resistance assay (UDS assay) in a routine diagnostic laboratory.. Study design - 50 plasma samples, previously characterized by population sequencing and that had shown ≥1 resistance associated mutation (RAM), were retrospectively tested by the UDS assay, including 18 B and 32 non-B subtypes; viral loads between 114-1,806,407 cp/ml; drug-naive (n = 27) and drug-experienced (n = 23) individuals.. Results - The UDS assay was successful for 37/50 (74%) samples. It detected all RAMs found by population sequencing at frequencies above 20%. In addition, 39 low-frequency RAMs were exclusively detected by the UDS assay at frequencies below 20% in both drug-naïve (19/26, 73%) and drug-experienced (9/18, 50%) ...
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KwaZulu-Natal (KZN) Province in South Africa has the highest HIV disease burden in the country, with an estimated population prevalence of 24.7%. A pilot sentinel surveillance project was undertaken in KZN to classify the proportion of adult patients failing first-line ART and to describe the patterns of drug resistance mutations (DRMs) in patients with virological failure (VF).VF in adults in KZN was
Two analogues of the nonnucleoside inhibitor of HIV-1 RT, MKC-442 (emivirine), containing different C6 substituents have been designed to be less susceptible to the commonly found drug-resistance mutation of Tyr181Cys. Compound TNK-6123 had a C6 thiocyclohexyl group designed to have more flexibility in adapting to the mutated drug-binding site. GCA-186 had additional 3,5-dimethyl substituents aimed at forming close contacts with the conserved residue Trp229. Both compounds showed approximately 30-fold greater inhibitory effect than MKC-442 to the Tyr181Cys mutant virus as well as to the clinically important Lys103Asn virus. X-ray crystallographic structure determination of complexes with HIV-1 RT confirmed the predicted binding modes. These strategies might be used to improve the resilience of other NNRTI series against common drug-resistance mutations.
PubMed comprises more than 27 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Urinary Tract Infection: Bacterial etiologies, drug resistance profile and associated risk factors among diabetic patients attending Nekemte Referral Hospital
If I had to guess, I would predict that you have developed resistance to sustiva (efavirenz). In general, I will continue treatment in patients waiting on drug resistance tests if their CD4 cell...
An NRTI or PI (reported with or without ritonavir) with a partially sensitive net assessment will not be considered fully sensitive 4. Mentally able to participate in the study 5. Men and women ≥ 18 years old - Women of child bearing potential who engage in vaginal intercourse and who are not clinically sterilized must use highly effective methods of birth control during the study Exclusion Criteria: 1. Screening HIV genotype showing presence at baseline of any of the following Protease inhibitor (PI) Mutation Patterns associated with genotypic resistance to Atazanavir sulfate/ Ritonavir or Darunavir/Ritonavir will lead to exclusion: 1. Subjects with any darunavir associated mutations* at baseline (*V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V) 2. Subjects with a major mutation to Atazanavir sulfate consisting of N88S 3. Subjects with more than 3 of any of the following Atazanavir sulfate related mutations:D30N, M36I/V, M46I/L/T, I54V/L/T/M/A, A71V/T/I/G, G73S/A/C/T, ...
A diarylpyrimidine derivative and REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 that is used in the treatment of HIV INFECTIONS. It is also used in combination with other ANTI-HIV AGENTS, since ANTIVIRAL DRUG RESISTANCE emerges rapidly when it is used alone ...
HIV drug resistance genotyping is a critical tool in the clinical management of HIV infections. Although resistance genotyping has traditionally been conducted using Sanger sequencing, next-generation sequencing (NGS) is emerging as a powerful tool due to its ability to detect low-frequency alleles. ...
Doctors can now boast of their first FDA-approved pill capable of treating drug-resistant HIV, which is possible only due to the creation of a new molecule by a researcher from Purdue University
Most of the current knowledge on antiretroviral (ARV) drug development and resistance is based on the study of subtype B of HIV-1, which only accounts for 10% of the worldwide HIV infections. Cumulative evidence has emerged that different HIV types, groups and subtypes harbor distinct biological properties, including the response and susceptibility to ARV. Recent laboratory and clinical data highlighting such disparities are summarized in this review. Variations in drug susceptibility, in the emergence and selection of specific drug resistance mutations, in viral replicative capacity and in the dynamics of resistance acquisition under ARV selective pressure are discussed. Clinical responses to ARV therapy and associated confounding factors are also analyzed in the context of infections by distinct HIV genetic variants.
Sequences will be selected using relationships within the Antibiotic Resistance Ontology, which may reflect simple membership (is_a) or biological processes such as regulation (regulates), evolution (derives_from), sub-units in protein complexes (part_of), drug targets (targeted_by, targeted_by_drug), or drug resistance (confers_resistance_to, confers_resistance_to_drug). In addition, AMR genes are part_of resistance mechanisms. For example, is_a can be used to download all TEM beta-lactamases but is_a and part_of used to download all efflux proteins, including sub-units. Adding regulates to an efflux search would additionally include regulatory proteins. At minimum, we recommend use of is_a and part_of for most downloads.. ...
Organisation profile:. The research team of Prof. Vandamme is investigating factors influencing antiviral treatment response in HIV infected patients with a special focus on the impact of virus drug resistance. The team is responsible for drug resistance testing in clinical practice at the local AIDS Reference Laboratory. Another research topic involves the evolution and molecular epidemiology of human viruses, seeking to understand in particular the origin and evolution of HIV and HTLV, the only two pathogenic human retroviruses known so far. Prof. Vandamme organizes the yearly International Bioinformatics Workshop on Virus Evolution and Molecular Epidemiology, in 2006 it will be 12 years (http://www.kuleuven.ac.be/aidslab/veme.htm). The research team of Professor Van Ranst works on the molecular epidemiology of rotaviruses, papillomaviruses, RSV, and enteroviruses. The team is also developing and testing a vaccine against hantaviruses. Other reserch projects investigate the host genetic ...
High Prevalence of Drug Resistance Mutations Among Patients Failing First-Line Antiretroviral Therapy and Predictors of Virological Response 24 Weeks After Switch to Second-Line Therapy in S o Paulo State, Brazil. ...
Stable disease may be annotated as a clinical response - not further specified where stable disease is considered by an author as a positive response to therapy and/or where stable disease has been followed by a relapse. Acquired resistance mutations will occur in tumours annotated as a resistant recurrence e.g. Imatinib clinical resistant recurrence. A recurrent tumour or a metastatic site has been screened for mutations following relapse after an initial drug response. Only those secondary mutations reported as proven to be associated with resistance or presumed by authors to be associated with resistance, e.g. based on their gene location, are annotated as acquired resistance mutations and not incidental passenger mutations detected in a recurrent tumour. Intrinsic resistance mutations will occur in tumours annotated as having a primary non response e.g. Imatinib clinical primary non response. Only those mutations reported as associated with resistance are annotated as primary resistance ...
The high proportion of individuals starting treatment with drug resistance already warrants changing the recommended first-line therapy.
Portland State University researchers have found that only about half the genes in a specific virus affecting single cell organisms is needed to infect a host. This means the virus can undergo major mutations without losing its ability to survive and infect.
"Improving Viral Protease Inhibitors to Counter Drug Resistance". Trends in Microbiology. 24 (7): 547-557. doi:10.1016/j.tim. ... Skoreński M, Sieńczyk M (2013). "Viral proteases as targets for drug design". Current Pharmaceutical Design. 19 (6): 1126-53. ... Southan C (July 2001). "A genomic perspective on human proteases as drug targets". Drug Discovery Today. 6 (13): 681-688. doi: ... They are therefore a common target for antiviral drugs.[13][14] Uses[edit]. Main article: Proteases (medical and related uses) ...
Stanford University Drug Resistance Database. Koziel MJ, Peters MG (2007). "Viral hepatitis in HIV infection". N Engl J Med. ... A better explanation of the data is that lamivudine continues to have a partial anti-viral effect even in the presence of the ... Other resistance mutations are L80V/I, V173L and L180M. Minor side effects may include nausea, fatigue, headaches, diarrhea, ... The drug can trigger an inflammatory response to opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. ...
Anti-viral drugs[edit]. Many nations, as well as the World Health Organization, are working to stockpile anti-viral drugs in ... There also is the potential of viruses to evolve drug resistance. Some H5N1-infected persons treated with oseltamivir have ... Peramivir is a pharmaceutical drug used to treat viral infections. Like zanamivir and oseltamivir, peramivir is a neuraminidase ... Other anti-viral drugs are less likely to be effective against pandemic influenza. ...
Yilmaz NK, Swanstrom R, Schiffer CA (July 2016). "Improving Viral Protease Inhibitors to Counter Drug Resistance". Trends in ... Skoreński M, Sieńczyk M (2013). "Viral proteases as targets for drug design". Current Pharmaceutical Design. 19 (6): 1126-53. ... doi:10.1007/s11947-010-0431-4. Southan C (July 2001). "A genomic perspective on human proteases as drug targets". Drug ... Blood clotting (such as thrombin) and viral polyprotein processing (such as TEV protease) requires this level of specificity in ...
"Improving Viral Protease Inhibitors to Counter Drug Resistance". Trends in Microbiology. 24 (7): 547-557. doi:10.1016/j.tim. ... Skoreński M, Sieńczyk M (2013). "Viral proteases as targets for drug design". Current Pharmaceutical Design. 19 (6): 1126-53. ... Southan C (July 2001). "A genomic perspective on human proteases as drug targets". Drug Discovery Today. 6 (13): 681-688. doi: ... Tong L (2002). "Viral Proteases". Chemical Reviews. 102 (12): 4609-4626. doi:10.1021/cr010184f. PMID 12475203.. ...
Her work on ABC transporters includes investigating their role in resistance to chemotherapy drugs; antigen presentation in ... adaptive immunity and viral infection; cystic fibrosis; and bacterial nutrition. In 2019, she was elected to the National ...
Major risk factors for HCMV drug resistance are the residual capacity of the host's immune system to control viral replication ... HCMV antiviral drug resistance can be detected by phenotypic or by genotypic drug resistance testing. Phenotypic resistance ... "A new tool linking human cytomegalovirus drug resistance mutations to resistance phenotypes". Antiviral Research. 85 (2): 318- ... of amino acid changes in the UL97 protein kinase and the viral DNA polymerase have been reported to cause drug resistance. ...
In Dubin-Johnson syndrome, a mutation in multiple drug-resistance protein 2 (MRP2) causes a rise in conjugated bilirubin. In ... In acute viral hepatitis, the GGT levels can peak at 2nd and 3rd week of illness, and remained elevated at 6 weeks of illness. ... Acute viral hepatitis usually has normal or increased ALP. For example, hepatitis A has increased ALP due to cholestasis ( ... Viral hepatitis can also cause the rise in conjugated bilirubin. In parenchymal liver disease and incomplete extrahepatic ...
"Use of viral resistance patterns to antiretroviral drugs in optimising selection of drug combinations and sequences". Drugs. ... and accordingly the drugs should not be administered together. Additionally, zalcitabine should not be used with other drugs ... History of an AIDS drug. "HIVID (zalcitabine) tablets" (PDF). M.D./alert. U.S. Food and Drug Administration. June 2006. ... Resistance to zalcitabine develops infrequently compared with other nRTIs, and generally only occurs at a low level. The most ...
"Use of viral resistance patterns to antiretroviral drugs in optimising selection of drug combinations and sequences". Drugs. 52 ... Drug resistance to didanosine does develop, though slower than to zidovudine (ZDV). The most common mutation observed in vivo ... "Didanosine Side Effects in Detail - Drugs.com". Drugs.com. Retrieved 2018-08-08. "VIDEX (didanosine): chewable/dispersible ... The related pro-drug of didanosine, 2′,3′-dideoxyadenosine (ddA), was initially synthesized by Morris J. Robins (professor of ...
"Genetic diversity among human immunodeficiency virus-1 non-B subtypes in viral load and drug resistance assays". Clinical ... In addition, HIV-1 genetic diversity limits the use of currently available viral load and resistance tests. The natural world ... gambiae mosquitoes to a population of Anopheles coluzziin mosquitoes resulted in a transfer of the beneficial resistance gene ...
Influenza viruses can show resistance to anti-viral drugs. Like the development of bacterial antibiotic resistance, this can ... Generally, anti-viral drugs work optimally when taken within a few days of the onset of symptoms. Certain drugs are used ... Wu J, Yan P, Archibald C (2007). "Modelling the evolution of drug resistance in the presence of antiviral drugs". BMC Public ... However, virus strains have emerged that show drug resistance to some classes of drug. The United States authority on disease ...
Given the importance of viral evolution to disease emergence, pathogenesis, drug resistance, and vaccine efficacy, it has been ... Myxomatosis (a viral disease of rabbits, caused by the myxoma virus) had been introduced to New Zealand in 1952, but failed to ... It can also be used on paraffin-embedded tissue samples to confirm the presence of Myxoma virus and identify the viral strain. ... While initial viral strains were highly virulent, attenuated strains were soon recovered from the field. These attenuated ...
... identify infection by obtaining the nucleic acid sequence of viral samples to identify the virus and antiviral drug resistance ... These drugs are only functional against IAV but are no longer recommended for use because of widespread resistance to them ... The viral life cycle begins by binding to a target cell. Binding is mediated by the viral HA proteins on the surface of the ... The viral genome is incorporated inside a viral envelope derived from portions of the cell membrane that have HA, NA, and M2 ...
Many drugs have been discovered to treat the disease but mutations in the virus and resistance to the drugs make development ... The viral genome is reversely transcribed into the DNA of the infected cell by viral reverse transcriptase, the DNA is then ... Resistance of INI corresponds to those of other ARV drugs. First IN resistance is caused by primary mutations that decrease INI ... Some mutations increase resistance to the drugs to a large extent than others. For example, one of the most common mutation ...
Cabozantinib: Drugs from the MRP2 inhibitor (Multidrug resistance-associated protein 2 inhibitors) family such as abacavir ... CBV-TP competes with the viral molecules and is incorporated into the viral DNA. Once CBV-TP is integrated into the viral DNA, ... "FDA Drug Safety Communication: Safety Review update of Abacavir and possible increased risk of heart attack". Food and Drug ... "Abacavir". Drug Information Portal. U.S. National Library of Medicine. "Abacavir sulfate". Drug Information Portal. U.S. ...
December 2008). "Mechanism of Antiviral Drug Resistance of Vaccinia Virus: Identification of Residues in the Viral DNA ... Polymerase Conferring Differential Resistance to Antipoxvirus Drugs". Journal of Virology. 82 (24): 12520-12534. doi:10.1128/ ... HMPO-DAPy is an experimental antiviral drug. Gammon, Don B.; Snoeck, Robert; et al. ( ... Recent highlights in the development of new antiviral drugs v t e. ...
... may prove to be a valuable component for combination therapy and may help to prevent the apparition of drug resistance. Long- ... an enzyme that plays a critical role in viral maturation by initiating the processing of the N-linked oligosaccharides of viral ... Although generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with ... Celgosivir has a novel mechanism of action (preventing the glycosylation of viral proteins by the host), and demonstrates broad ...
This methodology was used to map viral glycoproteins, plaque morphology, and drug resistance markers, and to construct a ... He defined the structure of viral chromatin during latent infection of neurons and the mechanisms by which viral DNA is kept ... Orzalli, Megan H.; Knipe, David M. (2014). "Cellular Sensing of Viral DNA and Viral Evasion Mechanisms". Annual Review of ... to the viral replication compartments and that some of these inhibit viral replication while some are essential for viral ...
Viral resistance to the drug leads to the drug becoming useless since the virus evolves to have cells that are able to resist ... This fear of viral resistance caused a lot of users to be wary of the drug.[5] ... There were higher CD4 cell counts and less viral load in patients assigned to the three-drug group, proving that a three-drug ... Viral resistance[edit]. Many people were skeptical of being too hopeful with indinavir due to previous events that occurred ...
... often associated with amino acid substitutions that confer upon the virus a robust drug resistance without impairing the viral ... The potential HCV resistance against DAA drugs is a concern. Among the HCV quasispecies there are pre-existing variants with ... Recently, the central role of NS5A in viral proliferation has made it the target for drug development. As a result, new ... Shorter therapies with milder side effects would yield greater adherence, and the ever present spectre of drug resistance is ...
Drug resistance is a serious clinical concern in treatment of viral infection, and it is a particularly difficult problem in ... Resistance mutations are known for all approved NRTIs. Two main mechanisms are known that cause NRTI drug resistance: ... Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs. In the summer of 1981 ... Between HIV Drug Resistance and RNase H", Viruses, 2 (7): 1476-1503, doi:10.3390/v2071476, PMC 2982141, PMID 21088701 Kirby, K. ...
Non-adherence of HIV antiretroviral therapy increases the risk of drug suppression and resistance (Bangsberg, D. R., Moss, A. R ... even for individuals who have reached complete viral suppression, by confirmed rebound of viral load above 400 copies / ml. ... Bangsberg, David R.; Moss, Andrew R.; Deeks, Steven G. (2004-05-01). "Paradoxes of adherence and drug resistance to HIV ... It is characterized by a confirmed viral load above 400 copies / ml after 24 weeks or above 50 copies / ml after 48 weeks of ...
In the herpes virus, drugs mainly target the viral DNA polymerase. As a result, mutations in the viral DNA polymerase that make ... HIV drug resistance mutations figures FDA-Approved HIV Medicines CDC Explanation of Influenza Resistance Mutations. ... "HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing". PLOS ONE. 10 (12): ... There are five classes of drug that are used to treat HIV infection, and resistance mutations can effect the efficacy of these ...
... leading some scientists to express concern that these blips could allow the virus to develop drug resistance. The results of ... Ray researches the influence of viral evolution on viral pathogenesis, concentrating in particular on complex RNA viruses such ... "Genotypic analysis of HIV-1 drug resistance at the limit of detection: virus production without evolution in treated adults ... "Small increases or 'blips' in HIV levels do not signal mutations leading to drug-resistant HIV" Kieffer, T.; Finucane, M.; ...
... molecular epidemiology of viral pathogens, and drug-resistance testing. There are more than 2.3 million unique viral sequences ... the development of antiviral drugs to treat viral diseases is a comparatively recent development. The first such drug was ... Viruses portal Animal virology Astrovirology Category:Viral diseases Glossary of virology Introduction to viruses List of viral ... some viral infection might even be beneficial to the host. The lethal viral diseases are believed to have resulted from an " ...
... molecular epidemiology of viral pathogens, and drug-resistance testing. There are more than 2.3 million unique viral sequences ... Viral sequencing can also be used to estimate when a viral outbreak began by using a molecular clock technique. Medical ... Viral genomes can be based in DNA or RNA. RNA viruses are more time-sensitive for genome sequencing, as they degrade faster in ... Mykrobe predictor -Antibiotic resistance prediction for S. aureus and M. tuberculosis from whole genome sequence data Rapid ...
When treating infection, whether bacterial or viral, there is always a risk of the infectious agent to develop drug resistance ... The drug has also shown activity against viruses with common NNRTI resistance associated mutations and cross-resistance ... The perfect anti-HIV drug chemical should be effective against drug resistance mutation. Understanding the target RT enzyme and ... mechanism of drug action and the consequence of drug resistance mutations provide useful information which can be helpful to ...
The antiviral drugs amantadine and rimantadine inhibit a viral ion channel (M2 protein), thus inhibiting replication of the ... Hurt AC, Ho HT, Barr I (October 2006). "Resistance to anti-influenza drugs: adamantanes and neuraminidase inhibitors". Expert ... Typically, biologics do not target metabolic pathways like anti-viral drugs, but stimulate immune cells such as lymphocytes, ... The central core contains the viral RNA genome and other viral proteins that package and protect this RNA. RNA tends to be ...
... meningitis and other viral haemorrhagic fevers may resemble EVD.[1] Blood samples are tested for viral RNA, viral antibodies or ... "U.S. Food and Drug Administration (FDA).. *Ebola: What You Need to Know - Scientific American articles related to Ebola; note ... with more than 1,000 cases and insecurity continuing to being the major resistance to providing an adequate response.[215][216] ... "U.S. Food and Drug Administration (FDA) (Press release). 14 October 2020. Retrieved 14 October 2020.. This article incorporates ...
"Drug Trials Snapshots: Aklief". U.S. Food and Drug Administration (FDA). 11 October 2019. Archived from the original on 19 ... Andriessen A, Lynde CW (November 2014). "Antibiotic resistance: shifting the paradigm in topical acne treatment". Journal of ... Aslam I, Fleischer A, Feldman S (March 2015). "Emerging drugs for the treatment of acne". Expert Opinion on Emerging Drugs. 20 ... Aslam I, Fleischer A, Feldman S (March 2015). "Emerging drugs for the treatment of acne". Expert Opinion on Emerging Drugs ( ...
Drug risks[edit]. Filgrastim is typically dosed in the 10 microgram/kg level for 4-5 days during the harvesting of stem cells. ... This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly one in 1000 people of ... "A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea" ... Immunosuppressive drugs are given for a minimum of 6-months after a transplantation, or much longer if required for the ...
"Infection and Drug Resistance. 8: 119-128. doi:10.2147/IDR.S66739. PMC 4440423. PMID 26028977.. ... Unlike viral meningitis, Lyme lymphocytic meningitis tends to not cause fever, last longer, and recur.[33][30] Lymphocytic ... The EM (Erythema migrans) rash is often accompanied by symptoms of a viral-like illness, including fatigue, headache, body ... A hexavalent (OspA) protein subunit-based vaccine candidate VLA15 was granted fast track designation by the U.S. Food and Drug ...
Figueiredo LT (2009). "Viral pneumonia: epidemiological, clinical, pathophysiological and therapeutic aspects". J Bras Pneumol ... "Community-Acquired Pneumonia: From Common Pathogens To Emerging Resistance". Emergency Medicine Practice. 7 (12).. Unknown ... "Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis". CMAJ : Canadian Medical ... Ruuskanen, O; Lahti, E, Jennings, LC, Murdoch, DR (2011-04-09). "Viral pneumonia". Lancet. 377 (9773): 1264-75. doi:10.1016/ ...
From Genetic resistance to malaria: "Where this parasite [p. falciparum] is endemic, young children have repeated malaria ... The medical community did not know the natural history of yellow fever, a viral infection spread by the Aedes aegypti mosquito ... After experimenting, Rush decided that a powder of ten grains of calomel (mercury) and ten grains of the cathartic drug jalap ( ... and anything else that might lower their resistance. Vinegar and camphor in infected rooms "cannot be used too frequently upon ...
Research foci: drug resistance; cancer genomics; tumor microenvironment; growth control in mammalian cells; transcriptional and ... A.D. Hershey and Martha Chase, "Independent Functions of Viral Protein and Nucleic Acid in Growth of Bacteriophage," J. General ... In 2011, Christopher Vakoc discovers an important new drug target, BRD4, for a lethal form of Acute Myelogenous Leukemia (AML); ... In 2014, Phase 3 trials begin for drug to treat spinal muscular atrophy (SMA), a neurodegenerative disease, based on Adrian ...
"Journal of Food and Drug Analysis. 26 (2): S61-S71. doi:10.1016/j.jfda.2018.01.009. ISSN 1021-9498. PMID 29703387.. [permanent ... Hybrids with kumquats (× Citrofortunella) have good cold resistance. A citrus tree in a container may have to be repotted every ... Also rather important are the viral infections to which some of these ectoparasites serve as vectors such as the aphid- ... "Journal of Food and Drug Analysis. 25 (1): 71-83. doi:10.1016/j.jfda.2016.11.008. ISSN 1021-9498. PMID 28911545.. [permanent ...
... drug resistance - drug-drug interaction - DSMB - Duffy antigen system - dysplasia - dyspnea ... viral burden - viral core - viral culture - viral envelope - viral load - viremia - viricide - virion - virology - virus - ... antiretroviral drugs - antisense drugs - antitoxins - Antiviral drug - aphasia - aphthous ulcer - apoptosis - approved drugs - ... multi-drug rescue therapy - multiple drug-resistant tuberculosis (MDR-TB) - mutation - myalgia - mycobacterium - mycobacterium ...
"Fluoroquinolone Antibacterial Drugs: Drug Safety Communication - FDA Advises Restricting Use for Certain Uncomplicated ... People with COPD can experience flare-ups that are often triggered by a viral or bacterial respiratory infection.[100] The ... Concerns include the potential for antibiotic resistance and side effects including hearing loss, tinnitus, and changes to the ... Seeking the Prometheus effect". Current Drug Targets. 14 (2): 246-52. doi:10.2174/1389450111314020009. PMID 23256721.. ...
The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the ... However these drugs can quickly become ineffective due to the fact that the gene sequences that code for the protease and the ... and resistance to exogenous retroviral infection. Endogenous retroviruses have also received special attention in the research ... This step will also make viral enzymes and capsid proteins (8). Viral RNA will be made in the nucleus. These pieces are then ...
... the first active drug on heart rate (Dacorene) or the first synthetic no-depolarising muscle relaxant (Flaxedil). The discovery ... a great pharmacy for the Resistance thanks to the initiative of Vallery-Radot, Pasteur's nephew. The Germans became suspicious ... serum which was able to agglutinate the bacteria and neutralize the toxin was supplied by a horse inoculated with the viral ... and from which emerged numerous drugs, among which one can mention the first pentavalent arsenical treatment (Stovarsol), the ...
11.0 11.1 11.2 Ruuskanen, O; Lahti, E; Jennings, LC; Murdoch, DR (2011-04-09). "Viral pneumonia". Lancet 377 (9773): 1264-75. ... "Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis". CMAJ : Canadian Medical ... "Community-Acquired Pneumonia: From Common Pathogens To Emerging Resistance". Emergency Medicine Practice 7 (12). Archived from ...
Artursson P (1990). "Epithelial transport of drug in cell culture. I: A model for studying the passive diffusion of drugs over ... 2009). "Silencing the breast cancer resistance protein expression and function in Caco-2 cells using lentiviral vector-based ... viral transfection research, and lipid transport.[5] ... Artursson P & Karlsson J (1991). "Correlation between oral drug ... Shah P, Jogani V, Bagchi T, Misra A (2006). "Role of Caco-2 cell monolayers in prediction of intestinal drug absorption". ...
... resistance to fluoroquinolones among the bacteria that cause urinary infections has been increasing.[42] The Food and Drug ... Rarely they may be due to viral or fungal infections.[23] Healthcare-associated urinary tract infections (mostly related to ... "Food and Drug Administration (FDA). 8 March 2018. Archived from the original on 18 July 2019. Retrieved 17 July 2019.. ... Aronson, edited by Jeffrey K. (2008). Meyler's side effects of analgesics and anti-inflammatory drugs. Amsterdam: Elsevier ...
Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 in humans had increased to 91% by 2005. ... H3N2 is a subtype of the viral genus Influenzavirus A, which is an important cause of human influenza. Its name derives from ... Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in ... "U S Food and Drug Administration Home Page". 2019-08-27.. *^ "WHO recommends new B strain for next season's flu vaccine". ...
2002). "Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand". J. Acquir. Immune. Defic. Syndr ... 2000). "Antiretroviral resistance during successful therapy of human immunodeficiency virus type 1 infection". Proc. Natl. Acad ... Chigwedere P, Seage GR, Gruskin S, Lee TH, Essex M (October 2008). "Estimating the Lost Benefits of Antiretroviral Drug Use in ... Blankson JN, Persaud D, Siliciano RF (2002). "The challenge of viral reservoirs in HIV-1 infection". Annu. Rev. Med. 53: 557- ...
... drug resistance, virologic failure: evolving concepts". Infectious disorders drug targets 11 (2): 167-74. PMID 21406048.. ... xunto co xenoma viral, dentro da partícula vírica. O ADN viral resultante é despois importado ao núcleo celular e intégrase no ... A carga viral dunha persoa infectada é un importante factor de risco na transmisión por vía sexual e de nai a fillo.[44] ... Gráfico que mostra a relación entre o número de copias de VIH ou carga viral (en vermello en copias de ARN por mL de plasma) e ...
negative regulation of viral genome replication. • humoral immune response. • positive regulation of interleukin-8 production. ... Victor FC, Gottlieb AB (2002). "TNF-alpha and apoptosis: implications for the pathogenesis and treatment of psoriasis". J Drugs ... It also induces insulin resistance by promoting serine-phosphorylation of insulin receptor substrate-1 (IRS-1), which impairs ... On other tissues: increasing insulin resistance. TNF phosphorylates insulin receptor serine residues, blocking signal ...
As of 2009, none have been both found effective and licensed for use.[46] There are ongoing trials of the antiviral drug ... Antibiotics have no effect against viral infections and thus have no effect against the common cold.[43] Antibiotics are often ... The use of antibiotic prescriptions has implications for antibiotic resistance.[63] An estimated 22 million to 189 million ... Expert opinion on drug safety 9 (2): 233-42. doi:10.1517/14740330903496410. PMID 20001764. ...
Seibert C, Sakmar TP (2004). „Small-molecule antagonists of CCR5 and CXCR4: a promising new class of anti-HIV-1 drugs". Curr. ... tableau of resistance or susceptibility to HIV infection?". Adv. Dent. Res. 19 (1): 49-51. PMID 16672549. doi:10.1177/ ... and internalization in viral-cell fusion and as targets for entry inhibitors". Biochim. Biophys. Acta. 1614 (1): 51-61. PMID ... Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene". Nature. ...
Certain disorders like narcolepsy, are best treated with prescription drugs such as modafinil.[13] Others, such as chronic and ... Upper airway resistance syndrome. *Restless leg syndrome. *Periodic limb movement disorder. *Circadian rhythm sleep disorders * ...
Whilst drug resistance typically involves microbes chemically inactivating an antimicrobial drug or a cell mechanically ... Viral disease. Notes and references[edit]. *^ "Archived copy" (PDF). Archived (PDF) from the original on 2016-08-03. Retrieved ... In addition to drugs being specific to a certain kind of organism (bacteria, fungi, etc.), some drugs are specific to a certain ... stopping the uptake of a drug, another form of drug resistance can arise from the formation of biofilms. Some bacteria are able ...
... to develop viral resistance in 98% of those tested after 28 days and 85% still showed resistance after one year.[58] However, 8 ... though the drug mechanism for improving viral arthritis is unclear.[19] Prognosis[edit]. The mortality rate of chikungunya is ... viral antigen and viral RNA were found in macrophages in the synovial joint of a person experiencing a relapse of ... Viral replication is highly cytopathic, but susceptible to type-I and -II interferon.[43] In vivo, in studies using living ...
... including a common mutation that confers drug resistance (with William Pao[18]); and generation of numerous mouse models of ... Their discovery triggered the identification of many other cellular proto-oncogenes-progenitors of viral oncogenes and targets ... Director, Office of National Drug Control Policy. Gil Kerlikowske. 2009-14. Angella Reid. 2011-17. Michael Botticelli. 2014-17 ...
Seruga B, Ocana A, Tannock IF (January 2011). "Drug resistance in metastatic castration-resistant prostate cancer". Nature ... Viral infection. Papilloma virus has been proposed in several studies to have a potential role in prostate cancer, but as of ... "FDA approves new drug for advanced prostate cancer" (Press release). Food and Drug Administration. 15 May 2013. Archived from ... "U.S. Food and Drug Administration. 2011-04-28. Archived from the original on 2013-09-22.. ...
Brüssow, H. (2012). "On Viruses, Bats and Men: A Natural History of Food-Borne Viral Infections". Viruses: Essential Agents of ... The second and third digits go along the wing tip, allowing the wing to be pulled forward against aerodynamic drag, without ... In most mammals, the walls of the veins provide mainly passive resistance, maintaining their shape as deoxygenated blood flows ... Instead, more diverse groups had greater viral diversity.[187]. They seem to be highly resistant to many of the pathogens they ...
Antibiotic resistance. Main article: Antibiotic resistance in gonorrhea. Many antibiotics that were once effective including ... Emergence of multi-drug resistant Neisseria gonorrhoeae (PDF) (Report). World Health Organisation. 2012. p. 2. Archived from ... "Antibiotic-resistant gonorrhoea on the rise, new drugs needed". World Health Organization. 7 July 2017. Archived from the ... "Gonorrhoea treatment resistance risk falls but new diagnoses rise". Health Protection Agency. 12 September 2012. Archived from ...
Your doctor is certainly correct on this question of viral blips. Your last... ... Ask the Experts > Forum on HIV Drug Resistance > Q & A Viral blips. Jun 15, 2004 I have been HIV+ for exactly one year and 6 ... Your last viral load was 119. Remember that a significant change in viral load is a 0.5 log or greater change, i.e. a greater ... Six days later I had another test done and my viral load was undetectable. My doctor and I attibuted the blip to a bad case of ...
I would hope that your viral load would be undetectable. Given your past antiretroviral use, I would be very concerned that you ... Read More About HIV/AIDS Drug Resistance Browse Forums: <-- Select . Aging. Choosing Your Meds. En Español. In Italiano. ... or maintain suppression for long if your viral load does drop below 50). You do not want to develop resistance to sustiva while ... Viral Load Detectable. Jul 30, 2001 Dear Dr. Little Hiv+ since 03/97 vl 50k, tcells 350, started on azt,3tc,viracept, was ...
... ... HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow. Mark Mascolini. Viral load upon switching to a 2-drug ... A GSS of 1.0 indicates viral susceptibility to the regimen, 0.5 indicates possible resistance, and 0 indicates resistance [2]. ... HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow. Abstract P299.. 2. Villacian J. Basics of HIV resistance testing ...
Therapeutic Drug Monitoring and Viral Resistance Testing in the Treatment of HIV-Infected Children. The safety and scientific ... Therapeutic Drug Monitoring and Viral Resistance Testing in the Treatment of HIV-Infected Children. ... If not enough of the drug is found in the blood, the dose of the drug will be increased and the amount of the drug in the blood ... monitoring drug blood levels to make sure there is enough drug to work against the virus, and changing the drug dose if it is ...
Field Evaluation of Dried Blood Spots for Routine HIV-1 Viral Load and Drug Resistance Monitoring in Patients Receiving ... Field Evaluation of Dried Blood Spots for Routine HIV-1 Viral Load and Drug Resistance Monitoring in Patients Receiving ... Field Evaluation of Dried Blood Spots for Routine HIV-1 Viral Load and Drug Resistance Monitoring in Patients Receiving ... Field Evaluation of Dried Blood Spots for Routine HIV-1 Viral Load and Drug Resistance Monitoring in Patients Receiving ...
HIV Drug Resistance Study Highlights Need for Viral Load Tests, Affordable Second-Line Treatments. ... NNRTI Resistance Found in 12% of People Stopping Treatment With Undetectable Viral Load: Implications for Stock-Outs ... Authors of the study, Pretreatment HIV Drug Resistance Increases Regimen Switches in Sub-Saharan Africa, note that the numbers ... Transmitted Drug Resistance: The Other Side to the PrEP Failure Case Were Not Talking About ...
Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds ... Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally ... Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally ... Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds. PLoS ...
A key driver of resistance is that drug resistance mutations often persist even in the absence of drugs and despite the fact ... A key driver of resistance is that drug resistance mutations often persist even in the absence of drugs and despite the fact ... Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS ONE. 2009; 4:e4724. doi: ... Persistence of Transmitted HIV-1 Drug Resistance Mutations Associated with Fitness Costs and Viral Genetic Backgrounds Download ...
HIV drug resistance study highlights need for viral load tests, affordable second line treatments. By Antigone Barton on ... more than twice the cost of first-line drugs - and for third-line drugs - about 15 times the cost of first-line drugs - that ... Authors of the study, Pretreatment HIV Drug Resistance Increases Regimen Switches in Sub-Saharan Africa, note that the numbers ... New TB drug approval a milestone, all agree - with caveats, some add. The announcement Wednesday of U.S. Food and Drug ...
HIV-1 drug resistance profiles in children and adults with viral load of . In: Journal of the American Medical Association. ... HIV-1 drug resistance profiles in children and adults with viral load of . Journal of the American Medical Association. 2001; ... HIV-1 drug resistance profiles in children and adults with viral load of . / Hermankova, Monika; Ray, Stuart Campbell; Ruff, ... title = "HIV-1 drug resistance profiles in children and adults with viral load of", ...
The role of the HIV-1 reverse transcriptase mutation H208Y to drug resistance and viral fitness. Doctoral thesis , UCL ( ... The role of the HIV-1 reverse transcriptase mutation H208Y to drug resistance and viral fitness ... The role of the HIV-1 reverse transcriptase mutation H208Y to drug resistance and viral fitness. ... Accessory mutations are thought to arise alongside major or primary drug resistance mutations in order to augment resistance, ...
... ... Mutations at gag cleavage sites (CS) have been found to correlate with resistance mutations in protease (PR). Therefore, it is ... In this study, 30 subtype-C infected second-line failures were genotyped using the ViroSeqTM resistance genotyping kit and the ... only 16 had resistance mutations in PR and 23 in gag. The most frequent major PI mutations were: I54V/L, M46I, V82A, and I84V ...
US label changes for rilpivirine and Eviplera follows EU caution on high baseline viral load: new summary on drug resistance. 1 ... US label changes for rilpivirine and Eviplera follows EU caution on high baseline viral load: new summary on drug resistance. ... Table 1: Rilpivirine resistance by baseline viral load. VL ,100,000 copies/mL. VL ,100,000 copies/mL. ... Of note, the FDA review included a different summary of data relating to the risk of resistance based on baseline viral load ...
Antiretroviral drug resistance and viral tropism in HIV-1 CRF06_cpx infected patients failing antiretroviral (ARV) therapy. ... HIV-1 DRMs and tropism were detected using Stanford University Drug Resistance Database and Geno2pheno[coreceptor] 2.5. ... Aim: to describe HIV-1 drug resistance mutations (DRMs) and co-receptor tropism in antiretroviral (ARV) treatment failing ... Median viral load at the time of tropism testing was 53,326 (IQR 16,328-113,018) and median CD4+ count 184 (IQR 142-217) cells/ ...
The international peer-reviewed journal covering the global spread and threat of multi-drug resistant clones of major pathogens ... Viral Immunology Viral Immunology. The only journal reporting on all aspects of the rapidly growing field of viral immunology, ... Microbial Drug Resistance (MDR) is an international, peer-reviewed journal that covers the global spread and threat of multi- ... Microbial Drug Resistance is under the editorial leadership of Editor Alexander Tomasz, PhD, The Rockefeller University, ...
CD4 count and viral load are important indicators of health status. Learn what they measure and how they affect HIV treatment ... Drug resistance. Another reason for regular viral load tests is to monitor any drug resistance to the prescribed HIV therapy. ... Maintaining a low viral load reduces the risk of developing resistance to the therapy. A healthcare provider can use viral load ... What is a viral load?. An HIV viral load test measures the number of HIV particles in a milliliter (mL) of blood. These ...
The international peer-reviewed journal covering the global spread and threat of multi-drug resistant clones of major pathogens ... Viral Immunology Viral Immunology. The only journal reporting on all aspects of the rapidly growing field of viral immunology, ... with comprehensive coverage of immune responses to viral infections from basic mechanisms to clinical applications. ...
How Drug Resistance Arises. By Douglas D. Richman. Viral-Load Tests Provide Valuable Answers. ...
HIV drug resistance report 2017  World Health Organization; Global Fund; US Centers for Disease Control and Prevention (‎2017 ... Technical and operational considerations for implementing HIV viral load testing: interim technical update. ... 2014)‎. Technical and operational considerations for implementing HIV viral load testing: interim technical update. World ...
Drug resistance. A healthcare provider may also order tests to learn if a strain of HIV is resistant to any medications used in ... Viral load. Viral load is a measure of the amount of HIV in the blood. A healthcare provider can measure the viral load to ... U.S. Food and Drug Administration (FDA). approved the OraQuick In-Home HIV Test. Its the first rapid test for HIV that can be ... When a persons viral load is low or undetectable, theyre less likely to develop stage 3 HIV or experience its associated ...
... cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies. In: ... cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies. Journal ... cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies. Journal ... cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies, ...
HIV drug resistance has the potential to become a serious emerging threat to the roll-out of antiretroviral treatment ... Viral load testing is another tool which the WHO supports to monitor viral load and identify potential drug resistance, ... What drives HIV drug resistance?. HIV drug resistance can arise from a range of different factors, which can be split up into ... What is HIV drug resistance?. HIV drug resistance occurs when the virus starts to make changes (mutations) to its genetic make- ...
HIV Macromolecular Interactions and Impact on Viral Evolution of Drug Resistance Olson, Arthur J. Scripps Research Institute, ... implications of viral macromolecular interactions and dynamics and its broader impacts of the evolution of drug resistance. The ... We will explore resistance evolution in HIV as an opportune platform upon which to characterize the dynamic relationships ... HIV enzymes with their partners and effectors since they encompass key processes in the viral life cycle and as existing drug ...
... Login ... Insertions and Deletions in HIV-1 Reverse Transcriptase: Consequences for Drug Resistance and Viral Fitness. Menéndez-Arias, ... However, the development of drug resistance constitutes a major hurdle towards long-term efficacy of those therapies. With the ... The frequently found combination of a dipeptide insertion and thymidine analogue resistance mutations (i.e. T215Y) in the viral ...
"While today, we are powering surveys for HIV recency and incidence; drug resistance; antiretroviral therapy; and viral-load ... Since 2016, Marc has been on loan from CDCs Division of Viral Hepatitis as team leader of the Global Hepatitis Programme at ... Summarizing the importance of both treatment and PMTCT programs, he says the early discovery that treatment suppresses viral ... CDC/Emory South African Study Provides Compelling New Evidence on Role of Transmission in Drug-Resistant TB Epidemics ...
A new report found high rates of HIV drug resistance among HIV-infected MSM. What are the implications for HIV care among this ... The study site, viral load, drug resistance mutations, and resistance patterns for 44 individuals who had high-level resistance ... Table 1. Patterns of HIV drug resistance. Case. Study site. Log10 VLa Major drug resistance mutations. High-level resistance. ... Conclusion: High prevalence of drug resistance was observed among MSM. Some had multiclass resistance, resistance to drugs used ...
RITM halts HIV drug resistance, viral load testing to focus on COVID-19. April 06, 2020 BY: Daphne Galvez ... Advocacy group appeals to govt: Support continued, uninterrupted access to HIV drugs. March 20, 2020 BY: Katrina Hallare ...
geno2pheno[ngs-freq]: a genotypic interpretation system for identifying viral drug resistance using next-generation sequencing ... geno2pheno[ngs-freq]: a genotypic interpretation system for identifying viral drug resistance using next-generation sequencing ...
Participants did not show evidence of drug resistance, those with virological failure did not experience a change in HIV ... In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal ... Biktarvy Suppresses HIV Well in Women and Those With Drug Resistance. Gilead Sciences Biktarvy (bictegravir/tenofovir ... Taking drugs for a period of time after an infection has been treated, to stabilise the condition or prevent a re-occurrence or ...
Causes of viral rebound can include drug resistance, poor adherence to an HIV treatment regimen or interrupting treatment. ... drug resistance. A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs ... Eight cases of drug resistance occurred in the study, seven in the efavirenz arm. Three participants in the efavirenz arm ... They had acquired resistance to an NNRTI either through sexual transmission of drug-resistant virus, through exposure to ...
  • Given your past antiretroviral use, I would be very concerned that you may not suppress fully (or maintain suppression for long if your viral load does drop below 50). (thebody.com)
  • Objective: To determine genetic resistance profiles of low-level plasma HIV-1 in patients with prolonged viral suppression (+ T cells and plasma H IV for 7 of 10 patients and showed patient-specific clustering of sequences and a close relationship between virus in te plasma and the latent reservoir. (elsevier.com)
  • Conclusions: Based on the samples that could be amplified, low-level viremia in children and adults receiving HAART with prolonged suppression of viremia to less than 50 copies/mL of HIV-1 RNA may result primarily from archival, pre-HAART virus, reflecting earlier treatment conditions, and does not appear to require development of new, HAART-selected mutations reflecting partial resistance to therapy. (elsevier.com)
  • To analyze HIV drug resistance among MSM recruited for participation in the HPTN 078 study, which evaluated methods for achieving and maintaining viral suppression in HIV-infected MSM. (medscape.com)
  • In the United States, the current administration's plan, 'Ending the HIV Epidemic: A Plan for America', includes interventions such as early antiretroviral therapy (ART) to achieve viral suppression and preexposure prophylaxis (PrEP). (medscape.com)
  • HPTN 078 evaluated an HIV prevention strategy focused on achieving and maintaining viral suppression in HIV-infected MSM in the United States (screening/enrollment: 2016-2017). (medscape.com)
  • Subcutaneous injections of PRO 140, a monoclonal antibody that blocks HIV entry into cells, was well tolerated and maintained undetectable viral load for more than a year after stopping antiretroviral therapy (ART) in people with viral suppression, according to a study presented at the ASM Microbe 2016 meeting last week in Boston. (aidsmap.com)
  • In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy. (aidsmap.com)
  • Paul Maddon, a scientific advisor at CytoDyn, presented findings from a phase 2b trial of PRO 140 as maintenance therapy for people who had achieved viral suppression on standard combination ART. (aidsmap.com)
  • Among the 28 patients in the cohort assessing longer-term treatment, 15 people who maintained viral suppression for 12 weeks were trained to self-administer their shots and allowed to continue PRO 140 maintenance therapy for an additional 108 weeks in an extension phase. (aidsmap.com)
  • All participants who restarted ART regained full viral suppression. (aidsmap.com)
  • Using more durable regimens is likely to improve viral suppression in sub-Saharan Africa and reduce the prevalence of drug resistance over time. (aidsmap.com)
  • Purpose of this survey was to estimate prevalence of viral load (VL) suppression and emergence of HIV drug resistance (HIVDR) among individuals receiving antiretroviral therapy (ART) for 36 months or longer in Vietnam using a nationally representative sampling method. (who.int)
  • Present survey was one of the first to describe viral load suppression and ADR using nationally representative sample following new WHO guidance. (who.int)
  • Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study. (cdc.gov)
  • Pattern of improvement in adherence from ART initiation till viral re-suppression. (cdc.gov)
  • For young people, maintaining viral suppression can be a struggle. (aidsmap.com)
  • Factors that are associated with the development of drug resistance include use of monotherapy, inadequate suppression of viral replication, nonadherence to ART drugs, and initiation of therapy late in the course of HIV infection [ 4 ]. (hindawi.com)
  • Viral load tests are used to monitor the effects ART, to track viral suppression, and detect treatment failure. (wikipedia.org)
  • Up until recently, my viral load has remained undetectable and my CD-4's have risen from a low of 129, when seroconverting, to around 450. (thebody.com)
  • However, my labs done in March showed a detectable viral load of 520 copies. (thebody.com)
  • Six days later I had another test done and my viral load was undetectable. (thebody.com)
  • What is concerning me is my most recent labs, taken last week, show a detectable viral load of 119 copies. (thebody.com)
  • Your last viral load was 119. (thebody.com)
  • Remember that a significant change in viral load is a 0.5 log or greater change, i.e. a greater than 3-fold change from the previous value. (thebody.com)
  • I am very concerned of the erros in the past of keeping a detectable viral load. (thebody.com)
  • I share your concern - after 8 months on sustiva , ziagen , and zerit , I would hope that your viral load would be undetectable. (thebody.com)
  • I would suggest that you talk to your physician and express your concern about your viral load. (thebody.com)
  • Viral load upon switching to a 2-drug antiretroviral regimen and a genotypic susceptibility score (GSS) estimating number of fully active antiretrovirals in the new regimen proved the best predictors of virologic failure with the new 2-drug combo [1]. (natap.org)
  • Everyone had a preswitch genotype and at least 1 postswitch viral load measure. (natap.org)
  • The analysis included 2149 switchers with a median age of 50, a median CD4 count of 577, and a median viral load of 1.57 log (under 40 copies). (natap.org)
  • Almost three quarters of participants (71%) had a baseline viral load below 50 copies, so most of these people were not switching from a failing regimen to 2 drugs. (natap.org)
  • Median time since last viral load above 50 copies stood at 3 years (interquartile range [IQR] 1 to 6). (natap.org)
  • Multivariate analysis to pinpoint predictors of virologic failure adjusted for antiretroviral regimen, viremia copy-years (a cumulative measure of time with a detectable viral load), CD4 count nadir, and GSS found that only viral load independently predicted failure. (natap.org)
  • Every 10-fold higher viral load at the switch almost doubled the odds of failure (adjusted odds ratio [aHR] 1.81, 95% confidence interval [CI] 1.38 to 2.38, P (natap.org)
  • The researchers concluded that in antiretroviral-experienced people switching to a 2-drug regimen, higher viral load at the switch and having less than 1 fully active drug in the new regimen (GSS below 1) "strongly influence virologic efficacy" of the 2-drug combination. (natap.org)
  • The viral load will also be measured and additional tests to determine whether the resistance pattern of the patients' virus has changed. (clinicaltrials.gov)
  • Dried blood spots (DBS) can be used in developing countries to alleviate the logistic constraints of using blood plasma specimens for viral load (VL) and HIV drug resistance (HIVDR) testing, but they should be assessed under field conditions. (asm.org)
  • The findings, published in Clinical Infectious Diseases , underscore needs for greater access in Africa to testing to monitor patients' viral load as a measure of treatment effectiveness, and to more affordable second-line HIV treatments, authors noted. (thebodypro.com)
  • he never talks about how he got it, why he never told me, but I took over his giving him the tablets on a certain time every day, his meals have gone to extremely healthy and his last test a month ago has reflected his viral load is non existant. (thebodypro.com)
  • While monitoring patients' viral loads is considered the best way to confirm that treatment is working, access to viral load testing remains limited across Africa, the authors note. (sciencespeaksblog.org)
  • On 7 December 2012, the US FDA approved changes to the rilpivirine ( Edurant ) package insert that included restricting the indication to treatment-naïve adult patients with HIV viral load less than 100,000 copies/mL. (i-base.info)
  • Of note, the FDA review included a different summary of data relating to the risk of resistance based on baseline viral load and CD4 count, that appears to be different to the analysis of the 96 week pooled phase 3 data in the EU Summary of Product Characteristics, see Table 1 and 2. (i-base.info)
  • This showed that in people failing virologically, there were disproportionately higher rates of resistance when stratified by both baseline viral load (above vs below 100,000 copies/mL) and baseline CD4 count (above vs below 200 cells/mm3). (i-base.info)
  • These results highlight the lower response rates for people with the most advanced HIV disease, defined by baseline viral load, due to the higher potential for clincially important drug resistance. (i-base.info)
  • Median viral load at the time of tropism testing was 53,326 (IQR 16,328-113,018) and median CD4+ count 184 (IQR 142-217) cells/cmm. (biomedcentral.com)
  • CD4 vs. Viral Load: What's in a Number? (healthline.com)
  • If someone has received an HIV diagnosis, there are two things they'll want to know: their CD4 count and their viral load. (healthline.com)
  • What is a viral load? (healthline.com)
  • An HIV viral load test measures the number of HIV particles in a milliliter (mL) of blood. (healthline.com)
  • A high viral load may indicate a recent HIV transmission, or HIV that's untreated or uncontrolled. (healthline.com)
  • A viral load can include millions of copies per mL of blood, especially when the virus is first contracted. (healthline.com)
  • A low viral load indicates relatively few copies of HIV in the blood. (healthline.com)
  • If an HIV treatment plan is effective, a person will be able to maintain a lower viral load. (healthline.com)
  • There's no direct relationship between CD4 count and viral load. (healthline.com)
  • However, in general, a high CD4 count and a low - or undetectable - viral load are desirable. (healthline.com)
  • The lower the viral load, the likelier it is that HIV therapy is working. (healthline.com)
  • When HIV remains untreated, the CD4 count decreases and the viral load increases. (healthline.com)
  • A healthcare provider will likely conduct CD4 counts and viral load tests more often at the beginning of HIV therapy or with any changes in medications. (healthline.com)
  • More frequent testing may be needed for some people, such as those in their first two years of treatment or those whose viral load isn't suppressed. (healthline.com)
  • Less frequent testing may be needed for people who take daily medication or have maintained a suppressed viral load for over 2 years. (healthline.com)
  • A single CD4 or viral load test result only represents a snapshot in time. (healthline.com)
  • The time of day, any illnesses, and recent vaccinations can all affect CD4 count and viral load. (healthline.com)
  • Regular viral load tests, not CD4 counts, are used to determine the effectiveness of a person's HIV therapy. (healthline.com)
  • The goal of HIV therapy is to reduce or suppress the viral load to an undetectable level. (healthline.com)
  • According to HIV.gov , HIV viral load is typically undetectable below levels of 40 to 75 copies/mL. (healthline.com)
  • These are temporary, oftentimes small increases in viral load. (healthline.com)
  • A healthcare provider will monitor the viral load more closely to see if it returns to an undetectable level without any change in therapy. (healthline.com)
  • Another reason for regular viral load tests is to monitor any drug resistance to the prescribed HIV therapy. (healthline.com)
  • A viral load test that directly measures the virus can be used to detect whether someone has recently acquired HIV. (healthline.com)
  • The two most common measures for assessing HIV transmission are CD4 count and viral load . (healthline.com)
  • Increasing access to viral load testing, and monitoring of other clinical factors relating to patient care, patient behaviour, and clinic and programme management can mitigate the rise of HIVDR. (avert.org)
  • These new mutations make copies of themselves, gradually increasing the level of the virus (viral load) in the person living with HIV - meaning treatment may no longer be effective. (avert.org)
  • 8 This is when viral load may become higher and detectable - and the prescribing healthcare provider would consider switching out a different drug or drug class. (avert.org)
  • Some studies have reported decreases in acquired drug resistance in high-income countries, [ 6 , 7 ] which may reflect increased use of drugs with high genetic barriers for resistance and increased use of HIV genotyping and viral load monitoring to guide treatment. (medscape.com)
  • Previous studies showed that a single intravenous injection of PRO 140 dramatically reduced HIV levels, and weekly subcutaneous (under the skin) injections reduced viral load significantly more than placebo. (aidsmap.com)
  • The CD01 study included 39 HIV-positive adults with exclusively CCR5-tropic HIV (according to the Trofile DNA Co-receptor Tropism Assay), viral load below 40 copies/ml on a stable ART regimen and a CD4 T-cell count above 350 cells/mm 3 . (aidsmap.com)
  • Among people tested with a single-copy HIV RNA assay, the lowest median viral load was 0.4 copies/ml. (aidsmap.com)
  • 400 copies/ml) and restarted ART, while one relocated and left the study with an undetectable viral load at 47 weeks. (aidsmap.com)
  • A South African survey conducted in 2017 found that one-in-six South Africans tested in a door-to-door sampling study had a detectable viral load and NNRTI resistance. (aidsmap.com)
  • The 90-90-90 target is that 90% of all people living with HIV will have been diagnosed, 90% of all people with known HIV infection will be receiving antiretroviral therapy (ART), and 90% of all people receiving ART will have a suppressed viral load. (scielosp.org)
  • Moreover, the greatest change in viral load was seen for rtM204I without hepatitis B e antigen (HBeAg). (nih.gov)
  • Is the Subject Area "Viral load" applicable to this article? (plos.org)
  • From ART initiation, the proportion of patients with adherence ≥90% increased steadily from 54% at first high viral load (VL) to 67% at confirmed VF, and 81% at time of re-suppressed VL. (cdc.gov)
  • The current study compared dried fluid spot specimens with the reference standard plasma specimens as a practical tool for viral load (VL) and HIVDR genotyping in resource-limited settings. (cdc.gov)
  • Importantly, this method can be applied to both viral RNA and proviral DNA amplification templates, allowing genotyping in HIVinfected subjects with suppressed viral load (e.g., subjects on ART). (krisp.org.za)
  • The long-range HIV genotyping from proviral DNA was successful in about 90% of 212 targeted blood specimens collected in a cohort where the majority of patients had suppressed viral load, including 65% of patients with undetectable levels of HIV-1 RNA load. (krisp.org.za)
  • demographic characteristics, information of ART , CD4+ T cell counts, viral load (VL) and HIV drug resistance of a total of 8 362 patients were collected. (bvsalud.org)
  • Multi-variables non-conditional logistic regression model was used to study the relationship between viral load , HIV drug resistance and CD4+ T cell counts. (bvsalud.org)
  • In the case of low viral load , the most vulnerable were the NNRTI antiviral drugs such as EFV and NVP. (bvsalud.org)
  • Viral rebound and emergence of drug resistance in the absence of viral load testing: a randomized comparison between zidovudine-lamivudine plus Nevirapine and zidovudine-lamivudine plus Abacavir. (ox.ac.uk)
  • Median viral load was 4.5 log10 copies/ml with a median CD4 cell count of 197 (IQR: 47-359) cells/mm3. (aidsmap.com)
  • The typical course of untreated HIV‐1 infection showing the change in CD4 cell counts (blue line) and plasma HIV‐1 RNA levels ('viral load', red line) over time. (els.net)
  • Welcome to the Viral Load Monitoring training. (washington.edu)
  • To more effectively treat HIV clients, Zimbabwe has adopted viral load testing to monitor ART treatment outcomes. (washington.edu)
  • This training will explain the different algorithms that guide decisions on when to test viral load and what kind of counselling and treatment to provide based on the test results. (washington.edu)
  • Session 1 provides an overview of viral load monitoring in Zimbabwe. (washington.edu)
  • In Session 3, you'll learn how to interpret test results and what to do for clients with high viral load. (washington.edu)
  • Results: CEAT-HBV identified 79/183 (43%) patients with non-adherence to antiviral treatment and among them, 53/79 (67%) were more frequently viral load positive. (usp.br)
  • Greater access to Antiretroviral drugs (ARVs) is good news, but it has magnified the need for HIV viral load monitoring to properly administer these drugs. (mynewsdesk.com)
  • A recent Médecins Sans Frontières (MSF) review of data from 12 low- and middle-income countries found that only 2% of patients had ever received a HIV viral load test result, no less received them every 6-months as recommended by the World Health Organization (WHO). (mynewsdesk.com)
  • One Hope by Joe Average was used for the XI International AIDS Conference in Vancouver in 1996The direct benefits of HIV viral load testing to the patient are well documented in terms of better outcomes with decreased mortality. (mynewsdesk.com)
  • That's why HIV viral load testing has long been a standard part of treatment in middle- to upper-income nations. (mynewsdesk.com)
  • But if we look beyond the patient, there is an equally compelling public health case to be made for ensuring access to HIV viral load testing in the low- and middle-income countries where the vast majority of HIV patients live. (mynewsdesk.com)
  • Here are four ways HIV viral load testing protects the public as well as the patient. (mynewsdesk.com)
  • With HIV viral load monitoring the clinic can identify noncompliant patients early and more efficiently target counseling only to those who need it. (mynewsdesk.com)
  • Monitoring viral load helps identify viral activity and address it before the treatment fails and the patient needs to be moved to a new treatment (if available). (mynewsdesk.com)
  • Without viral load measurement, doctors can also misattribute patient symptoms to treatment failure and switch them before it is required. (mynewsdesk.com)
  • Studies have found that transmission among HIV-infected persons with a viral load below 1,500 copies/ml is rare. (mynewsdesk.com)
  • So managing HIV viral load can, in itself, contribute to prevention. (mynewsdesk.com)
  • This is where HIV viral load monitoring contributes. (mynewsdesk.com)
  • A 2010 study in resource-limited settings found that in the absence of HIV viral load monitoring, the incidence of drug-resistant mutations following treatment failure is high. (mynewsdesk.com)
  • Kinetics of hepatitis B viral load during 48 weeks of treatment with 600 mg vs 100 mg of lamivudine daily. (washington.edu)
  • The development of this TW10-specific CD8 + T cell response is associated with the reduction of viral load by 1,000-fold or more. (rupress.org)
  • A previous study of anti-a4b7 treatment in acute SIV infection found that it could not only suppress viral load, but also keep treated animals healthy for years, while control animals' SIV infection progressed to AIDS diseases. (healthcanal.com)
  • In this study we examined the genotypic, phenotypic and fitness correlates associated with the development of Q151M MDR in the absence of viral load monitoring. (pubmedcentralcanada.ca)
  • Viral load monitoring for HIV is the regular measurement of the viral load of individual HIV-positive people as part of their personal plan for treatment of HIV/AIDS. (wikipedia.org)
  • A count of the viral load is routine before the start of HIV treatment. (wikipedia.org)
  • Various viral load tests might be used. (wikipedia.org)
  • Viral load monitoring is used by HIV-positive people to develop a plan for their personal treatment of HIV/AIDS. (wikipedia.org)
  • If the treatment is not changed, then viral load is monitored with testing every 3-4 months to confirm a stable low viral load. (wikipedia.org)
  • Patients who are medically stable and who have low viral load for two years may get viral load counts every 6 months instead of 3. (wikipedia.org)
  • If a viral load count is not stable or sufficiently low, then that might be a reason to modify the HIV treatment. (wikipedia.org)
  • If HIV treatment is changed, then the viral load should be tested 2-8 weeks later. (wikipedia.org)
  • Previous treatment guidelines recommended that anyone with a viral load greater than 100,000 copies/mL of blood should begin treatment. (wikipedia.org)
  • Successful combination ART should give a fall in viral load of 1.5 to 2 logs (30-100 fold) within six weeks, with the viral load falling below the limit of detection within four to six months. (wikipedia.org)
  • Laboratory monitoring schedule for patients using ART: Viral load monitoring for HIV complements the CD4 count, which is another sort of test associated with monitoring HIV. (wikipedia.org)
  • The results of a viral load test help determine when a CD4 count is indicated. (wikipedia.org)
  • A CD4 test quantifies Helper T cells and is often combined with viral load testing to monitor the progression of HIV. (wikipedia.org)
  • A decreased CD4 count, in combination with higher numbers on a viral load test, indicates an increased risk of getting sick from opportunistic diseases. (wikipedia.org)
  • citation needed] While receiving ART some patients with undetectable viral load measurements may experience an increase in viral load, to a low level (usually below 400 copies/mL blood), and then returned to an undetectable level. (wikipedia.org)
  • Viral load blips are partially explained by various patient related factors, and thought to be relatively common. (wikipedia.org)
  • High level and sustained increases in viral load are frequently related to the development of drug resistance and/or viral mutations, and often dictate changes in ART. (wikipedia.org)
  • Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation. (uzh.ch)
  • This persistence behavior was associated with the predicted fitness cost of a given resistance mutation in the particular genetic background in which it occurred. (prolekare.cz)
  • This thesis characterises the H208Y mutation in terms of linkage of H208Y to other major and accessory resistance mutations, and examines two phenotypic aspects, drug susceptibility and viral fitness. (ucl.ac.uk)
  • The HIV Resistance Database held at the Royal Free Hospital was searched for genotypes containing the H208Y mutation. (ucl.ac.uk)
  • A viral mutation can occur at any stage of this process. (avert.org)
  • For some drugs, such as the NRTI lamivudine and all NNRTIs, just one mutation - notably the M184V or K103N mutations - can result in high-level drug resistance. (avert.org)
  • Overall, 84.9% of patients had ≥1 resistance mutation, 80% had ≥1 nucleoside reverse transcriptase inhibitor mutation, 71.4% had ≥1 non-nucleoside reverse transcriptase inhibitor mutation and 31.7% had ≥1 protease inhibitor mutation. (scielosp.org)
  • Resistance can develop when antimicrobials are used to treat an infection and a mutation or change occurs in one of the microorganism's genes. (labtestsonline.org)
  • HIV mutates frequently - even in the absence of drug treatment - but not every mutation causes resistance to antiretroviral drugs. (labtestsonline.org)
  • If HIV is allowed to remain active in the presence of drugs meant to suppress it, then it is just a matter of time before it will produce a viable mutation that will be resistant to the drug. (mynewsdesk.com)
  • Genotypic testing is preferred over phenotypic resistance testing to guide therapy in persons with suboptimal virologic response or virologic failure while on first- or second-line regimens and in individuals in whom resistance mutation patterns are known or not expected to be complex (AII) . (nih.gov)
  • The addition of phenotypic to genotypic resistance testing is recommended for persons with known or suspected complex drug-resistance mutation patterns (BIII) . (nih.gov)
  • Quasispecies result from high mutation rates as mutants arise continually and change in relative frequency as viral replication and selection proceeds. (wikipedia.org)
  • High mutation rates and quasispecies were verified for other RNA viruses based on dissection of viral populations by molecular or biological cloning, and sequence analysis of individual clones. (wikipedia.org)
  • The only journal reporting on all aspects of the rapidly growing field of viral immunology, with comprehensive coverage of immune responses to viral infections from basic mechanisms to clinical applications. (liebertpub.com)
  • Surprising' research from Conference on Retroviruses and Opportunistic Infections (CROI) shows drug resistance does not impact test-and-treat roll-out in South Africa - at least in the short term. (avert.org)
  • The acyclic nucleoside phosphonate (ANP) family of drugs shows promise as therapeutics for treating poxvirus infections. (neb.com)
  • Infections caused by these drug-resistant viruses in mice were still treatable with higher concentrations of the ANPs. (neb.com)
  • Representing a major addition to the world literature on the subject, Viral Infections and Global Change explores trends of paramount concern globally, regarding the emergence and reemergence of vector-borne and zoonotic viruses. (wiley.com)
  • Viral Infections and Global Change is an indispensable resource for research scientists, epidemiologists, and medical and veterinary students working in ecology, environmental management, climatology, neurovirology, virology, and infectious disease. (wiley.com)
  • Although there are now effective diagnostic procedures that allow a safe blood supply in most developed countries, intravenous drug abuse continues to lead to new infections. (nature.com)
  • This is starkly obvious for antimicrobial drugs, with drug-resistant infections already responsible for well in excess of 100,000 deaths per year globally and a projected 10 million deaths per year by 2050 ( 4 ). (pnas.org)
  • As one of medicine's largest challenges, viral infections often escape vaccines due to their natural ability to mutate rapidly and develop drug resistance easily. (ibm.com)
  • IBM ) and Singapore's Institute of Bioengineering, Nanotechnology (IBN) announced they have identified a new breakthrough macromolecule that could help prevent deadly virus infections with a unique triple-play mechanism that can also help prevent viral drug resistance. (ibm.com)
  • Potential longer-term applications may include the development of a new mode of vaccination that could help prevent a whole category of viral infections. (ibm.com)
  • For instance, viral and cellular determinants of transmission have been defined, new mechanisms of innate anti-HIV resistance discovered, key differences between pathogenic and non-pathogenic HIV/SIV infections identified, immunopathogenic consequences of HIV infection elucidated and three-dimensional structures of critical cellular and viral proteins (and RNAs) deduced. (keystonesymposia.org)
  • Protein-protein interactions, which involve such key physiological actions as signal transduction and protein assembly, are highly desirable drug discovery targets, not only for HCV, but also for other viral infections because inhibitors of these protein associations have been shown to lack many clinical complications, such as the adverse side effects of recombinant therapeutic proteins. (scripps.edu)
  • To reduce the development of drug-resistant bacteria and maintain the effectiveness of KETEK and other antibacterial drugs, KETEK should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. (rxlist.com)
  • As 2-drug regimens gain popularity, clinicians need tools to help them predict which combinations will work best for which people. (natap.org)
  • Such tools would prove especially useful when picking a 2-drug medley for someone who has already taken 1 or more failing regimens and could have circulating or archived HIV resistant to individual antiretrovirals or entire antiretroviral classes. (natap.org)
  • Low-level viremia below 50 copies/mL may represent less of a concern regarding impending drug failure of current HAART regimens. (elsevier.com)
  • Therefore, it is important to collect data on subtype C protease and gag sequences from patients as these mutations may affect the efficacy of protease inhibitor (PI) containing drug regimens. (ukzn.ac.za)
  • With the increasing complexity of the antiretroviral regimens, novel mutational patterns conferring high-level resistance to nucleoside and nonnucleoside RT inhibitors have been identified in viral isolates. (mediu.edu.my)
  • These findings highlight the need for improved HIV care in this high-risk population, identification of alternative regimens for PrEP, and inclusion of integrase resistance testing when selecting ART regimens for MSM in the United States. (medscape.com)
  • About two-thirds of the patients with tenofovir-resistant strains also had become resistant to the other two drugs in their regimens, suggesting their treatment had become largely ineffective. (stanford.edu)
  • Resistance may develop when patients don't take their medication regularly, although it may also occur in adherent patients on some of the regimens used in the developing world. (stanford.edu)
  • Average percentage resistance to nucleoside reverse transcriptase inhibitor, protease inhibitor, full class resistance to nucleoside reverse transcriptase inhibitor, protease inhibitor and multidrug resistance increased in patients failing two or more regimens. (scielosp.org)
  • Also in RLS the rise in prevalence of TDR is mostly driven by NNRTI resistance, which is of particular concern as this drug class constitutes the foundation of current first-line ART regimens and prophylaxis for prevention of mother-to-child transmission. (springer.com)
  • Antiretroviral therapy (ART) is being administered in developing nations at unprecedented numbers following the World Health Organization's (WHO) development of standardized first-line drug regimens. (cdc.gov)
  • To ensure continued efficacy of these drug regimens, WHO recommends monitoring virological responses and development of human immunodeficiency virus (HIV) drug resistance (HIVDR) in HIV-infected patients in a prospective cohort. (cdc.gov)
  • A high proportion of adolescents and young adults living with HIV in Zimbabwe on failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens had clinically significant resistance mutations which could compromise the efficacy of a new regimen of tenofovir, lamivudine and dolutegravir, the 10th International AIDS Society Conference on HIV Science (IAS 2019) heard last week in Mexico City. (aidsmap.com)
  • Those on failing regimens have a high frequency of drug resistance mutations with limited affordable alternative treatment options. (aidsmap.com)
  • Increased resistance to NNRTIs and a need for simplified regimens led Zimbabwe to introduce dolutegravir with tenofovir and lamivudine (TLD), in single tablet form, in first-, second- and third-line regimens. (aidsmap.com)
  • Treatment regimens are mainly based on combinations of three antiretroviral agents with two different mechanisms of action, chosen from drug classes that target different steps in the virus replication cycle. (els.net)
  • When a person with HIV experiences virologic failure while receiving an INSTI-based regimen, genotypic testing for INSTI resistance (which may need to be ordered separately) should be performed to determine whether to include a drug from this class in subsequent regimens (AII) . (nih.gov)
  • ARV drugs used in first line ART regimens for adults and adolescents in the national ART program in India are Zidovudine, Tenofovir, Abacavir, Lamivudine, Efavirenz, and Nevirapine [ 2 ]. (hindawi.com)
  • Exploration of how this could be combined with anti-retroviral drug regimens is warranted. (healthcanal.com)
  • For example, it may present along the reverse transcriptase enzyme, meaning the efficacy of certain drugs or drug classes can be undermined - in this example, nucleoside/nucleotide reverse transcriptase inhibitors (NRTI/NtRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) drug classes. (avert.org)
  • [ 15 ] Resistance to integrase strand transfer inhibitors (INSTIs) was not observed in that cohort. (medscape.com)
  • In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as efavirenz is widespread in sub-Saharan Africa. (aidsmap.com)
  • Full class resistance to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and multidrug resistance were detected in 21.2%, 32.4%, 8% and 4.1% of patients, respectively. (scielosp.org)
  • Nevertheless, after 2011, a declining trend was observed in the frequency of multidrug resistance and full class resistance to nucleoside reverse transcriptase inhibitors and protease inhibitors. (scielosp.org)
  • The two amplicons cover critical regions across the HIV-1 genome (including pol and env), allowing analysis of mutations associated with resistance to protease inhibitors, reverse transcriptase inhibitors (NRTIs and NNRTIs), integrase strand transfer inhibitors, and virus entry inhibitors. (krisp.org.za)
  • In the 2000s, inhibitors of these enzymes and of another non-enzymatic but essential HCV protein (NS5A), referred to as direct acting antivirals (DAAs), emerged as the lead targets for HCV drug development. (nature.com)
  • Fusion of the viral and host cell membranes is blocked by fusion inhibitors. (els.net)
  • Reverse transcription of the viral RNA to double‐stranded DNA is targeted by nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs) and non‐nucleoside reverse transcriptase inhibitors (NNRTIs). (els.net)
  • Integration of the viral DNA is inhibited by integrase strand transfer inhibitors (InSTIs) and candidate allosteric integrase inhibitors (ALLINIs). (els.net)
  • Organosilane amine inhibitors were found to be generally as potent as their carbon analogues in targeting WT A/M2 and more potent against the drug-resistant A/M2-V27A mutant. (biomedsearch.com)
  • In addition, intermolecular NOESY spectra with dimethyl-substituted organosilane amine inhibitors clearly located the drug binding site at the N-terminal lumen of the A/M2 channel close to V27. (biomedsearch.com)
  • These drugs, collectively termed direct-acting antivirals (DAAs), include non-structural (NS) HCV protein inhibitors, NS3/4A protease inhibitors, NS5B RNA-dependent RNA polymerase inhibitors (nucleotide analogues and non-nucleoside inhibitors), and NS5A inhibitors. (mdpi.com)
  • Injecting drug user (IDU) has showed resistance to either nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) or nonnucleotide reverse transcriptase inhibitors (NNRTI). (hindawi.com)
  • The Q151M multi-drug resistance (MDR) pathway in HIV-1 reverse transcriptase (RT) confers reduced susceptibility to all nucleoside reverse transcriptase inhibitors (NRTIs) excluding tenofovir (TDF). (pubmedcentralcanada.ca)
  • Jupiter, FL, December 16, 2009 - Scientists from the Scripps Florida campus of The Scripps Research Institute and their colleagues at Boston University have described their discovery of several novel drug-like inhibitors of the hepatitis C virus (HCV). (scripps.edu)
  • Using a new fluorescence-based assay, the scientists were able to identify four small-molecule inhibitors of dimerization of the viral core protein. (scripps.edu)
  • GSS equals the sum of genotypic resistance scores for each drug in a regimen. (natap.org)
  • Predicting two-drug antiretroviral regimen efficacy by genotypic susceptibility score: results from a cohort study. (natap.org)
  • In 2009, a test for HIV-1 genotypic resistance was introduced in routine clinical practice in Cuba. (scielosp.org)
  • Burchell AN et al (2012) Increase in transmitted HIV drug resistance among persons undergoing genotypic resistance testing in Ontario, Canada, 2002-09. (springer.com)
  • HIVdb Program: Genotypic Resistance Interpretation Algorithm [Internet]. (who.int)
  • CONCLUSIONS: There was more extensive genotypic resistance in both treatment groups than is generally seen in resource-rich settings. (ox.ac.uk)
  • Plasma samples were obtained to HIV-1 genotypic resistance test. (usp.br)
  • Human immunodeficiency virus (HIV) genotypic antiretroviral drug resistance testing evaluates the likelihood that the HIV strain infecting an individual is resistant or has developed resistance to one or more antiretroviral therapy (ART) drugs. (labtestsonline.org)
  • With genotypic resistance testing, the genetic code of the HIV a person has been infected with is analyzed to determine if there are any genetic mutations that are known to cause ART resistance. (labtestsonline.org)
  • Genotypic, rather than phenotypic, testing is the preferred resistance testing to guide therapy in antiretroviral (ARV)-naive patients (AIII) . (nih.gov)
  • Standard genotypic drug-resistance testing in ARV-naive persons involves testing for mutations in the reverse transcriptase (RT) and protease (PR) genes. (nih.gov)
  • If transmitted integrase strand transfer inhibitor (INSTI) resistance is a concern, providers should ensure that genotypic resistance testing also includes the integrase gene (AIII) . (nih.gov)
  • Global prevalence of HIV drug resistance (HIVDR) is rising, mainly due to resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs - which make up the backbone of World Health Organization (WHO) first-line antiretroviral treatment regimes. (avert.org)
  • Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is an important target of drugs fighting HIV infection. (mediu.edu.my)
  • Prevalence of transmitted drug resistance was 11.4%, and 41% of mutated viruses exhibited dual-class resistance to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor. (scielosp.org)
  • We determined early viral changes (12 weeks) in YMDD mutants (rtM204I [YIDD sequence], rtM204V [YVDD]) and rtL180M in all 39 patients as well as amino acid changes in the polymerase reverse transcriptase (rt) region and precore/core promoter mutations in 15 patients who received long-term treatment (more than 1 year). (nih.gov)
  • To determine the genotype changes in HIV reverse transcriptase associated with in vitro AZT resistance to U-87201E. (clinicaltrials.gov)
  • The mean residual activity at week 48 was higher for abacavir in the presence of the typically observed resistance pattern of thymidine analogue mutations (TAMs) and M184V (1.47 log(10) copies/mL) than for nevirapine with M184V and nonnucleoside reverse-transcriptase inhibitor mutations, whether accompanied by TAMs (0.96 log(10) copies/mL) or not (1.18 log(10) copies/mL). (ox.ac.uk)
  • Among 37 isolates studied, 6 (16.2%) samples showed primary drug resistance (PDR) against reverse transcriptase (RT) inhibitor. (hindawi.com)
  • HIV is a retrovirus, an RNA virus that enters a host cell and uses the host DNA replication machinery and the enzyme reverse transcriptase to produce DNA from the viral RNA genome. (wikipedia.org)
  • The aim of ART is to limit HIV replication in the body, and different drug classes target different parts of this process - the HIV lifecycle - to stop HIV replicating and infecting all cells. (avert.org)
  • Understanding the structural interactions of HIV assembly, maturation, replication and integration is critical to extending the current structural knowledge o the three major AIDS drug targets to an understanding of their mechanisms in the viral lifecycle. (grantome.com)
  • By the end of 2017, there were more than 28,000 individuals living with HIV in Cuba, over 80% receiving antiretroviral therapy, which dramatically reduces viral replication, improves immune status and decreases risk of transmission. (scielosp.org)
  • Two enzymes encoded by HCV that are essential for viral replication - a serine protease (NS3-4A) and an RNA polymerase (NS5B) - are attractive drug targets. (nature.com)
  • The new macromolecule is composed of several specialized components to create a powerful triple-play action that helps fight viral infection and replication while inhibiting drug resistance. (ibm.com)
  • Neutralization - Another component of the macromolecule, known as basic amine groups, neutralize the pH inside the viral cell making it inhospitable for replication. (ibm.com)
  • A mix of multiple antiretroviral drugs has been recommended to suppress HIV replication, thus preventing HIV linked mortality and morbidity apart from enhancing the quality of life of HIV/AIDS infected people. (hindawi.com)
  • Because of fast rate of viral replication and lack of proof reading enzymes to correct errors occurring when virus converts its RNA into DNA via reverse transcription, HIV virus often makes mistakes in the copies, which may result in mutations and sometime mutations may lead to resistance against HIV drugs [ 5 ]. (hindawi.com)
  • A new study now demonstrates that multiple immune-driven sequence polymorphisms in the highly conserved HIV-1 Gag region of transmitted viruses are associated with reduced viral replication in newly infected humans. (rupress.org)
  • It is now well established that virus-specific immune responses, and in particular HIV-1-specific CD8 + T cell responses, contribute to the control of viral replication in infected individuals. (rupress.org)
  • But despite immune escape, viral replication remains well controlled in these individuals, and large numbers of individuals expressing HLA-B57 have long-term nonprogressive HIV-1 infection ( 16 ). (rupress.org)
  • The underlying factors responsible for this apparent paradox-efficient control of virus replication despite viral escape from CD8 + T cell-mediated immune pressure-appear to be related to the reduced replicative fitness of viruses containing escape mutations in the TW10 epitope. (rupress.org)
  • A GSS of 1.0 indicates viral susceptibility to the regimen, 0.5 indicates possible resistance, and 0 indicates resistance [2]. (natap.org)
  • Recombinant viruses containing patient derived RT genes with and without H208Y were constructed to examine the impact of H208Y on drug susceptibility and viral fitness. (ucl.ac.uk)
  • A multiple cycle drug susceptibility assay showed that H208Y conferred a reduced susceptibility to the nucleotide RT inhibitor tenofovir in the context of subtype B wild type RT and subtype B RT containing TAMs. (ucl.ac.uk)
  • and (c) comparing the anti-viral drug susceptibilities determined in step (a) and (b), wherein a decrease in anti-viral drug susceptibility at the later time compared to the first time indicates development or progression of anti-viral drug resistance in the patient. (epo.org)
  • Forty-six (81%) patients had full susceptibility to the three drugs in their first-line (1 L) regimen. (cdc.gov)
  • Conventional drug susceptibility testing (DST) can take 1-2 weeks once a positive culture has been obtained. (bmj.com)
  • Due to the high genetic variability of HCV, the outcome of DAA-based therapies may be altered by the selection of amino-acid substitutions located within the targeted proteins, which affect viral susceptibility to the administered compounds. (mdpi.com)
  • A major barrier to the long-term efficacy of ART is the emergence of drug resistant mutations in the polymerase gene of HIV-1, which reduces the susceptibility of the virus to antiretroviral (ARV) drugs. (hindawi.com)
  • Phenotypic drug susceptibility testing demonstrated that the Q151M-containing RT had reduced susceptibility to all NRTIs except for TDF. (pubmedcentralcanada.ca)
  • We demonstrate a complex interplay between drug susceptibility and replicative fitness in the acquisition Q151M MDR with serious implications for second-line regimen options. (pubmedcentralcanada.ca)
  • My doctor is not concerned about the detectable virus and says it's too low to cause resistance. (thebody.com)
  • This is determined by analyzing the virus's genotype (detailed genetic structure) and phenotype (response to exposure to anti-viral drugs). (clinicaltrials.gov)
  • Here we assessed the role of fitness-cost and the genetic background for resistance in a real-world epidemiological setting by studying the persistence behavior of transmitted antiretroviral resistance mutations of HIV. (prolekare.cz)
  • Overall our results underline the variability of persistence behavior as well as the important role of fitness costs and the genetic background in the evolution of antimicrobial resistance. (prolekare.cz)
  • This work reviews the genetic processes behind drug resistance. (hvivo.com)
  • HIV drug resistance occurs when the virus starts to make changes (mutations) to its genetic make-up (RNA) that are resistant to certain HIV drugs, or classes of HIV drugs. (avert.org)
  • Of concern in developed countries is the rising prevalence of mutations associated with NNRTI resistance, a drug class frequently used in first-line therapy which has a low genetic barrier for development of resistance. (springer.com)
  • However, it has been questioned whether the utility of these compounds could be compromised through the intentional genetic modification of viral sequences by bioterrorists or the selection of drug resistance viruses during the course of antiviral therapy. (neb.com)
  • In recent years, the use of assays for the genetic detection of mutations that confer resistance have been developed and evaluated. (bmj.com)
  • This is called "selective pressure" because the drug "selects" and allows the proliferation of the genetic forms of the microorganism that are resistant to it. (labtestsonline.org)
  • In this process, which is essential to the survival of the virus, the core protein binds to itself and related proteins to form the viral capsid, the outer lipid-encapsulated protein shell that protects the virus's genetic material like an eggshell protects its yolk sack. (scripps.edu)
  • J Clin Microbiol 50:3838?44, 2012), we developed a robust methodology for amplification of two large fragments of viral genome covering about 80% of the unique HIV-1 genome sequence. (krisp.org.za)
  • Genome wide analysis of hnRNP binding to HIV-1 RNA reveals a key role for hnRNP H1 in alternative viral mRNA splicing. (nih.gov)
  • It is well known that HIV-1 can rapidly develop drug resistance mutations when single sites in the viral genome are under intense selective pressure, such as in patients undergoing mono- and dual-drug therapy. (rupress.org)
  • The finding that a viral population was essentially a pool of mutants came at a time when mutations in general genetics were considered rare events, and virologists associated a viral genome with a defined nucleotide sequence, as still implied today in the contents of data banks. (wikipedia.org)
  • Your doctor is certainly correct on this question of viral blips. (thebody.com)
  • Intermediate HIV-1 Viremia (Blips) and Drug Resistance in Patients Receiving HAART. (washington.edu)
  • These transient blips do not indicate that the virus is developing resistance to drug therapy. (wikipedia.org)
  • HIV-infected children between 0 and 21 years of age who may benefit from treatment with a protease inhibitor and who are not benefiting from their current antiretroviral drug treatment regimen may be enrolled in this 48-week study. (clinicaltrials.gov)
  • Public health organizations and global funders have been very effective at expanding antiretroviral drug therapy to increasing proportions of patients in need," said Robert Shafer , MD, professor of medicine and co-author of the work. (stanford.edu)
  • Resistance to the commonly prescribed antiretroviral drug tenofovir is 'surprisingly common', according to findings published in the Lancet Infectious Diseases last week. (avert.org)
  • Thirteen (23%) were resistant to at least one antiretroviral drug but three were resistant to drugs not used in Nigeria. (cdc.gov)
  • DBS genotyping using in-house assays provides an alternative for antiretroviral drug resistance testing in children in resource-constrained regions but may require region-specific optimization before widespread use. (asm.org)
  • Among participants with virologic failure on their new regimen (defined as viral above 400 copies), the researchers used survival analysis to identify predictors of virologic failure. (natap.org)
  • Register your specific details and specific drugs of interest and we will match the information you provide to articles from our extensive database and email PDF copies to you promptly. (dovepress.com)
  • From the ARCA database ( https://www.dbarca.net/ ) the researchers selected antiretroviral-experienced people starting a 2-drug regimen from 2007 to 2017. (natap.org)
  • But as countries roll-out the latest 2017 World Health Organization (WHO) treatment guidelines that call for all people living with HIV to be on treatment 1 HIV drug resistance (HIVDR) has the potential to become a significant barrier to reaching the UNAIDS Fast-Track goal of ending AIDS by 2030. (avert.org)
  • Molecular epidemiology of hepatitis B virus mutants associated with vaccine escape, drug resistance and diagnosis failure. (bvsalud.org)
  • The massive implementation of the vaccine and antiviral agents against hepatitis B virus (HBV), targeting the envelope and viral polymerase genes , induces a selection pressure that might lead to the emergence of variants that impair the effectiveness of the vaccine, diagnostic methods and antiviral therapy . (bvsalud.org)
  • A stampede of recent clinical studies suggests that we are on the cusp of developing well-tolerated, orally delivered drugs that can effectively eradicate hepatitis C virus from most, if not all, infected individuals. (nature.com)
  • Unlike drug treatments for hepatitis B and HIV, most HCV researchers believe that this endpoint represents a durable cure that lowers the risk of progressive liver disease. (nature.com)
  • Mutations around interferon sensitivity-determining region: a pilot resistance report of hepatitis C virus 1b in a Hong Kong population. (biomedsearch.com)
  • AIM: To explore mutations around the interferon sensitivity-determining region (ISDR) which are associated with the resistance of hepatitis C virus 1b (HCV-1b) to interferon-α treatment. (biomedsearch.com)
  • Hepatitis B and C Viral Dynamics. (washington.edu)
  • Description: Hepatitis viral dynamics models, including effects of treatment. (washington.edu)
  • Hepatitis C virus dynamics in vivo: effect of ribavirin and interferon alfa on viral turnover. (washington.edu)
  • Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. (washington.edu)
  • Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon. (washington.edu)
  • Recent advances in molecular biology have led to the development of new antiviral drugs that target specific steps of the Hepatitis C Virus (HCV) lifecycle. (mdpi.com)
  • Viral loads are generally highest for a period right after contracting HIV. (healthline.com)
  • Changes in rtM204I and rtL180M viral loads were greater than that of the rtM204V, albeit statistically insignificant. (nih.gov)
  • [email protected]#To explore drug resistance of different viral loads, and investigate the relationship between drug resistance and CD4+ T cell counts in patients with HIV antiretroviral therapy ( ART ) in China from 2003 to 2015. (bvsalud.org)
  • Sydney Research Online: Assessment of drug resistance mutations in plasma and peripheral blood mononuclear cells at different plasma viral loads in patients receiving HAART. (edu.au)
  • However, 38% (70/183) had positive viral loads suggesting treatment non-response. (usp.br)
  • Higher viral loads . (rexhealth.com)
  • Patients with advanced disease were treated but many others were not, owing to the additional, often severe, side effects of this drug combination and the emergence of viral resistance. (nature.com)
  • The relationship between immune-mediated selection pressure, the emergence of viral escape mutations within targeted CD8 + T cell epitopes, and the impact of these mutations on viral replicative fitness is best illustrated in the context of virus-specific CD8 + T cell responses restricted by human histocompatibility leukocyte antigen (HLA)-B57. (rupress.org)
  • All these modes of cell-to-cell transfer are now considered as viral mechanisms to escape immune system and antiretroviral therapies, and could be involved in the establishment of persistent virus reservoirs in different host tissues. (frontiersin.org)
  • The immune system provides the body with resistance to disease. (encyclopedia.com)
  • For example, aged individuals often have attenuated or otherwise impaired immune responses to various bacterial and viral pathogens. (encyclopedia.com)
  • Prevention - Mannose (a type of sugar) components of the macromolecule bind directly to healthy immune cell receptors to help fight viral infection and allow the free flow of these naturally protective cells. (ibm.com)
  • To understand the complex interplay between the immune response and the sequence evolution of HIV-1, and to understand why sustained immune control of HIV-1 is so difficult to attain, it is important to examine the lessons learned from studies of HIV-1 drug resistance ( 4 ). (rupress.org)
  • Cloaking immune cells with antibodies that block T cell trafficking to the gut can substantially reduce the risk of viral transmission in a non-human primate model of HIV infection, scientists report. (healthcanal.com)
  • CD4 testing shows the strength of the immune system, but does not report viral activity. (wikipedia.org)
  • We conclude that if adherence is not assured, patients could exhibit virologic failure without having developed mutations associated with drug resistance. (cdc.gov)
  • To estimate the level of primary drug resistance among recently infected cases of HIV in 6 ART centres of North-Western India from September 2014 to June 2016. (hindawi.com)
  • Of 11 viruses 10 had resistance against two ARV classes (NRTI + NNRTI or NNRTI + INI) and 1 had triple class resistance (NRTI + NNRTI + PI). (biomedcentral.com)
  • They had acquired resistance to an NNRTI either through sexual transmission of drug-resistant virus, through exposure to nevirapine as treatment for prevention of mother-to-child HIV transmission or through failure of NNRTI-based treatment. (aidsmap.com)
  • Among 222 patients with VL 50-999 and HIVDR, the most frequent antiretroviral drugs were EFV and NVP, both of which were NNRTI, and whose percentage both were 94.1% (209 cases). (bvsalud.org)
  • Resistance to either NRTI or NNRTI among the recently is a new challenge that needs to be addressed. (hindawi.com)
  • The fact that both Y181C isolates are IDUs is important and represents 2/21 (~10%) NNRTI drug resistance. (hindawi.com)
  • The role of the protease cleavage sites in viral fitness and drug resistance in HIV-1 subtype C. (ukzn.ac.za)
  • Mutations at gag cleavage sites (CS) have been found to correlate with resistance mutations in protease (PR). (ukzn.ac.za)
  • O DNA pró-viral foi amplificado e seqüenciado para a região da protease e transcriptase reversa do vírus. (usp.br)
  • Picomolar to Micromolar: Elucidating the Role of Distal Mutations in HIV-1 Protease in Conferring Drug Resistance. (nih.gov)
  • Participants did not show evidence of drug resistance, those with virological failure did not experience a change in HIV tropism - allowing their virus to enter using CXCR4 instead of CCR5 co-receptors - and no-one developed antibodies against PRO 140. (aidsmap.com)
  • Dolutegravir is highly potent and virological failure resulting in drug resistance is rare. (aidsmap.com)
  • As transmitted drug resistance increases the risk of virological failure, current guidelines recommend to perform drug resistance testing at baseline in all newly diagnosed individuals to guide the choice of antiretroviral therapy. (springer.com)
  • In resource-limited settings (RLS), rollout of ART with limited virological monitoring frequently results in the risk of prolonged virological failure with selection and accumulation of drug resistance mutations and subsequent transmission of drug resistance. (springer.com)
  • BACKGROUND: We investigated virological response and the emergence of resistance in the Nevirapine or Abacavir (NORA) substudy of the Development of Antiretroviral Treatment in Africa (DART) trial. (ox.ac.uk)
  • The central concept here is pathogen fitness: whereas the resistant pathogen has a very strong advantage over the sensitive one in the presence of drug pressure, its disadvantages in the absence of treatment are typically weaker and can be compensated by other mechanisms such as compensatory mutations or selection at linked loci. (prolekare.cz)
  • The Journal addresses the serious challenges of trying to decipher the molecular mechanisms of drug resistance. (liebertpub.com)
  • Our approach is significant both for the promise of new structural insights into the interdependence of viral mechanisms, but also for the direct potential for new drug design methodologies and therapeutic strategies. (grantome.com)
  • Distribio Laboratoire de.Mechanisms of Antibiotic Resistance in the Microbial World. (slipcamgirls.ml)
  • Mechanisms may include expansion through proliferation of latently infected CD4 T cells without virus production and replenishment through ongoing virus production in body compartments where antiretroviral drugs have reduced penetration or activity. (els.net)
  • Context: The continued release of human immunodeficiency virus type 1 (HIV-1) into plasma at very low levels during highly active antiretroviral therapy (HAART) can be detected using specialized techniques, but the nature and significance of this low-level viremia, especially as related to acquisition of drug resistance mutations, are unclear. (elsevier.com)
  • While the prevalence of X4-tropic viruses in subtype B is relatively well studied the distribution of tropism in CRF06_cpx (causing Estonian epidemic) is less known, especially in the treatment experienced patients with established multidrug-resistance and who are candidates for therapy with CCR5 antagonist. (biomedcentral.com)
  • In a multivariate model, self-report of ever having been on antiretroviral therapy (ART) was associated with resistance ( P = 0.005). (medscape.com)
  • HIV resistance to the antiviral tenofovir , one of the mainstays of HIV treatment and prevention, is increasingly common following therapy, particularly in low and middle-income countries, according to a new, multi-national study. (stanford.edu)
  • Patients most at risk for tenofovir resistance were those who started therapy late in the progression of the disease or who received tenofovir in combination with drugs less commonly used in upper-income countries. (stanford.edu)
  • The prevalence of TDR varies among regions, risk groups, and drug classes due to different exposure to antiretroviral therapy (ART), risk behavior, and access to therapy. (springer.com)
  • Low prevalence of transmitted drug resistance of HIV-1 during 2008-2012 antiretroviral therapy scaling up in Southern Vietnam. (who.int)
  • Significantly improving the effectiveness of drug therapy of AIDS patients, Thomas Lengauer and his collaborators have developed bioinformatical models for predicting the resistance of HIV viral variants to applied drug combinations. (qld.gov.au)
  • This 2010 Falling Walls lecture video explores how his research has led to effective AIDS therapy, especially in the later stages of the disease, when the virus has evolved to high resistance. (qld.gov.au)
  • The second preferred therapy for a particular condition, used after first-line treatment fails or if a person cannot tolerate first-line drugs. (aidsmap.com)
  • Oseltamivir-resistance tests were not performed for these 8 patients because they all received oseltamivir therapy and their clinical symptoms resolved. (cdc.gov)
  • Session 4 discusses drug resistance and second-line therapy. (washington.edu)
  • How can you take your antiretroviral therapy drugs as prescribed? (rexhealth.com)
  • HIV drug-resistance testing is recommended at entry into care for persons with HIV to guide selection of the initial antiretroviral therapy (ART) regimen (AII) . (nih.gov)
  • Drug-resistance testing in the setting of virologic failure should be performed while the person is taking prescribed ARV drugs or, if that is not possible, within 4 weeks after discontinuing therapy (AII) . (nih.gov)
  • HIV primary drug resistance (PDR) is of great public health concern because it has the potential to compromise the efficacy of antiretroviral therapy (ART) at the population level. (hindawi.com)
  • When resistant mutations emerge because of drug selective pressure in individuals receiving antiretroviral therapy it is known as acquired resistance. (hindawi.com)
  • These studies also suggested that although viral escape from antiretroviral therapy through the development of drug resistance mutations may be immediately advantageous to the virus in the presence of the drug, they nonetheless result in a reduction of viral replicative fitness ( 4 ). (rupress.org)
  • Evidence for this fitness loss is derived in part from the observation that drug-resistance mutations quickly revert back to wild-type in the absence of the drug, either when therapy is stopped or when the virus is transmitted to a new host ( 5 , 6 ). (rupress.org)
  • Furthermore, continuing antiretroviral therapy even after the virus has developed resistance to a specific drug can be clinically beneficial ( 7 ). (rupress.org)
  • Due to the nature of the virus the drugs used to treat HIV are called antiretroviral medicines, and the course of treatment is called antiretroviral therapy (ART). (wikipedia.org)
  • A study across southern Africa following more than 2,700 people with HIV showed that before their treatment even began, more than 5 percent had viruses that were resistant to at least one of the first line of drugs used to treat HIV, necessitating a switch to a second, less accessible and more expensive treatment. (thebodypro.com)
  • While the study found that nearly 14 percent of the patients followed had HIV with drug-resistant mutations, genotyping of the viruses indicated that the drug-resistant strain had been transmitted in 5.5 percent of all cases. (thebodypro.com)
  • The authors, led by T. Sonia Boender of Amsterdam Institute of Global Health and Development, conclude that pretreatment resistance threatens sustainable HIV treatment success and highlights the need for improved access to tests to monitor treatment effectiveness and to affordable treatments for viruses not effectively treated with first-line medicines. (thebodypro.com)
  • After transmission, viruses with transmitted drug resistance mutations (TDRM) persist either as the dominant species or as minority variants, which are difficult to detect by population sequencing techniques [ 11 - 17 ]. (prolekare.cz)
  • Over time, due to mutations, the population of viruses in an individual may contain fewer viral strains susceptible to HIV treatment, and more strains that are drug resistant. (avert.org)
  • To address these concerns, vaccinia virus (strain Lederle) was passaged 40 times in medium containing an escalating dose of (S)-1-[3-hydroxy-2-(phosphonomethoxypropyl)-2,6-diaminopurine [(S)-HPMPDAP], which selected for mutant viruses exhibiting a approximately 15-fold-increased resistance to the drug. (neb.com)
  • These studies demonstrated a complex pattern of resistance, although as a general rule, the double-mutant viruses exhibited greater resistance to the deoxyadenosine than to deoxycytidine nucleotide analogs. (neb.com)
  • Phylogenetic (evolutionary) relationships among human immunodeficiency viruses type 1 (HIV‐1) and type 2 (HIV‐2) and simian immunodeficiency viruses (SIVs), including three main groups of HIV‐1 (M, N and O) and the recognised viral subtypes within group M (subtypes A-K). The phylogeny is based on amino acid sequences from the Pol protein. (els.net)
  • Also, by targeting both viral proteins and host−virus interactions, the antiviral macromolecule sidesteps the normal mutations that enable viruses to escape vaccines through the onset of resistance. (ibm.com)
  • With the recent outbreak of viruses such as Zika and Ebola, achieving anti-viral breakthroughs becomes even more important," said Dr. James Hedrick, lead researcher, advanced organic materials, IBM Research - Almaden, San Jose, Calif. "We are excited about the possibilities that this novel approach represents, and are looking to collaborate with universities and other organizations to identify new applications. (ibm.com)
  • We have created an anti-viral macromolecule that can tackle wily viruses by blocking the virus from infecting the cells, regardless of mutations. (ibm.com)
  • A viral quasispecies is a population structure of viruses with a large numbers of variant genomes (related by mutations). (wikipedia.org)
  • Troleandomycin was removed from the table of drug interactions and telithromycin was added with the clinical comment that telithromycin may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). (i-base.info)
  • We will focus on interactions of the major HIV enzymes with their partners and effectors since they encompass key processes in the viral life cycle and as existing drug targets provide a rich base of structural, biological and evolutionary data that will serve to infom our goals. (grantome.com)
  • We will study the mechanistic implications of viral macromolecular interactions and dynamics and its broader impacts of the evolution of drug resistance. (grantome.com)
  • Therefore, understanding the interactions between viral proteins and host cell proteins is very important to develop drugs for these liver diseases and HCC. (hindawi.com)
  • Attraction - One specialized component of the macromolecule enables strong hydrogen bonds with electrostatic interactions to attract the proteins on the virus surface -- disabling viral ability to infect healthy cells. (ibm.com)
  • Insertions of one, two or several residues appear to have a significant impact on nucleoside analogue resistance. (mediu.edu.my)
  • Reference: Mechanism of antiviral drug resistance of vaccinia virus: identification of residues in the viral DNA polymerase conferring differential resistance to antipoxvirus drugs. (neb.com)
  • More than 90 mutations have been identified in HIV-1 RT to be associated with resistance to RTIs, and the majority are clustered either around the polymerase active site or the hydrophobic binding pocket of NNRTIs in the DNA pol domain of RT [ 4 - 7 ]. (pubmedcentralcanada.ca)
  • Seven of the 11 patients had complications during treatment: 6 had viral or secondary bacterial pneumonia and 1 had acute respiratory distress syndrome (Table). (cdc.gov)
  • A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. (aidsmap.com)
  • To determine the genotype and phenotype effects of treatment with a nondideoxynucleoside agent on the alterations of the HIV-1 population associated with in vitro AZT resistance. (clinicaltrials.gov)
  • Blood specimens were also analyzed for drug resistant mutations using genotype tests. (ucsf.edu)
  • Methods The authors analysed the performance of a national UK molecular diagnostic service over a decade, based on the use of a line probe assay (Innolipa, LiPA) compared with conventional liquid and solid cultures with rapid molecular identification and culture-based drug resistance testing. (bmj.com)
  • Findings Data were available for 7836 consecutive patient samples using LiPA and the reference microbiological technique (conventional liquid and solid cultures with rapid molecular identification and culture-based drug resistance testing). (bmj.com)
  • Interpretation A molecular diagnostic service, using a non-automated line probe assay approach, provides a rapid and reliable national service for diagnosing MTBC and rifampicin resistance. (bmj.com)
  • However, the development of drug resistance constitutes a major hurdle towards long-term efficacy of those therapies. (mediu.edu.my)
  • This multi-pronged approach has been extremely successful at containing HIV-1, limiting the development of drug resistance, and dramatically slowing disease progression. (rupress.org)
  • Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus. (aidsmap.com)
  • Causes of viral rebound can include drug resistance, poor adherence to an HIV treatment regimen or interrupting treatment. (aidsmap.com)
  • We characterized their drug resistance mutations (DRM) and adherence profiles to learn how to better manage HIV drug resistance. (cdc.gov)
  • People that maintain excellent adherence to treatment enjoy long and healthy lives and are at little risk of developing drug resistance or transmitting the infection to contacts. (els.net)
  • Consistently high levels of adherence are required to prevent virus escape and emergence of drug resistance. (els.net)
  • Participants in the top two quintiles of adherence, who took 80 percent or more of their medications, accounted for more than half of all new drug resistance mutations occurring in the study. (ucsf.edu)
  • Only 12 percent of the new drug resistance mutations were found in the participants in the lowest adherence quintile, those who took less than 41 percent of their medications. (ucsf.edu)
  • Porém, 38% (70/183) tiveram carga viral positiva sugerindo não resposta ao tratamento. (usp.br)
  • A detectabilidade da carga viral antes da interrupção terapêutica foi o único fator associado com a resistência do vírus. (usp.br)
  • O aumento da carga viral, associado a comportamentos de risco, torna esses indivíduos uma fonte de cepas resistentes para a população, reforçando a necessidade de atenção especial para a prevenção da transmissão do HIV-1 nesse segmento de pacientes. (usp.br)
  • The item Breaking the Wall of Viral Drug Resistance : How Bioinformatics Can Help to Improve AIDS Therapies, Falling Walls Foundation, (electronic resource) represents a specific, individual, material embodiment of a distinct intellectual or artistic creation found in City Libraries, City of Gold Coast . (qld.gov.au)
  • Resistance mutations to anti-HIV medications are more likely to occur in patients who take most of their medications rather than in those who don't, according to AIDS specialists at the University of California, San Francisco. (ucsf.edu)
  • In this study, 30 subtype-C infected second-line failures were genotyped using the ViroSeqTM resistance genotyping kit and the gag region from these isolates were then characterised. (ukzn.ac.za)
  • To determine whether serial passage of patient pre-drug HIV isolates in the presence of U-87201E will generate the resistant mutants that may subsequently emerge in the patients. (clinicaltrials.gov)
  • The rapid identification of multidrug resistant tuberculosis (MDRTB) (ie, tuberculosis (TB) isolates resistant to at least isoniazid and rifampicin) reduces the time for the instigation of appropriate treatment, helps to reduce the spread of drug-resistant TB and may improve survival. (bmj.com)
  • 1 MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates known as PRSP ( penicillin -resistant Streptococcus pneumoniae ), and are isolates resistant to two or more of the following antibacterials: penicillin, 2 generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole. (rxlist.com)
  • This study will evaluate a new treatment strategy called therapeutic drug monitoring (TDM) in HIV-infected children and adolescents. (clinicaltrials.gov)
  • Authors of the study, Pretreatment HIV Drug Resistance Increases Regimen Switches in Sub-Saharan Africa , note that the numbers of people found to have acquired strains of HIV that do not respond optimally to one or more of medicines used to start treatment can be expected to grow, as more people start antiretroviral treatment in the next few years. (thebodypro.com)
  • In addition, because genotyping that led to classifying drug resistance as pretreatment relied on identifying known mutations, it is possible that more of the patients followed had strains of virus that were resistant before treatment but had not been identified. (thebodypro.com)
  • Though drug resistance prevalence has been shown to decrease or to stabilize in various industrialized countries due to successful ART, it still remains a major concern jeopardizing treatment success [ 2 , 3 ]. (prolekare.cz)
  • In addition, they point to costs for second line drugs - more than twice the cost of first-line drugs - and for third-line drugs - about 15 times the cost of first-line drugs - that will further stretch limited resources available for expanded HIV treatment access. (sciencespeaksblog.org)
  • However, the archival drug-resistant virus may be relevant regarding future treatment strategies. (elsevier.com)
  • The prevalence of H208Y in antiretroviral treatment naïve and treatment experienced patients was 5/3783 (0.1%) and 12/1304 (0.9%), respectively, indicating a high degree of conservation of position 208 in wild type virus and an increase in prevalence under selective drug pressure. (ucl.ac.uk)
  • Aim: to describe HIV-1 drug resistance mutations (DRMs) and co-receptor tropism in antiretroviral (ARV) treatment failing patients infected with HIV-1 CRF06_cpx and to establish their suitability to treatment with CCR5 receptor antagonists. (biomedcentral.com)
  • As 'Treat All' is rolled-out worldwide, the emergence of drug-resistant HIV has the potential to become a major public health threat, as it limits treatment options for people living with HIV. (avert.org)
  • 2018 WHO interim antiretroviral treatment guidelines now recommend dolutegravir-containing regimes as the preferred first-line treatment because of effectiveness and its high barrier to resistance. (avert.org)
  • Explore this page to find out more about what drug resistance is , how it affects treatment options , drug resistance as a public health threat , the prevalence of HIVDR , responding to HIVDR , and what the future holds . (avert.org)
  • The emergence of HIVDR has occurred due to multiple factors, including stock-outs of drugs, poor health service quality and treatment interruptions. (avert.org)
  • When antiretroviral treatment is given in inadequate levels, we are allowing for these drug resistant mutations to be selected out and multiplied to the point that drug resistant virus becomes the primary population in the viral pool. (avert.org)
  • The impact on treatment options for the patient depends on which viral mutations they have. (avert.org)
  • [ 1 ] Goals of this program and other programs for HIV treatment and prevention may be compromised by HIV drug resistance. (medscape.com)
  • While overall adverse events were common (more than 90% in the extension phase), there were no drug-related serious adverse events or treatment discontinuations for this reason. (aidsmap.com)
  • Investigate antiretroviral resistance and its relation to subtype distribution in HIV-1 treatment-naïve and previously treated patients in Cuba. (scielosp.org)
  • Resistance and HIV-1 subtype distribution were determined in 342 antiretroviral treatment-naïve patients and 584 previously treated for HIV-1 whose blood specimens were sent to the Pedro Kourí Tropical Medicine Institute during 2009-2014. (scielosp.org)
  • Detected levels of transmitted drug resistance highlight the need for a national surveillance study in treatment-naïve patients. (scielosp.org)
  • Barth RE et al (2012) Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients. (springer.com)
  • HIV is more proactively monitored among urban HIV patients than rural patients, and drug resistance and treatment failure is less prevalent. (avert.org)
  • Jordan MR, Bennett DE, Bertagnolio S, Gilks CF, Sutherland D. World Health Organization surveys to monitor HIV drug resistance prevention and associated factors in sentinel antiretroviral treatment sites. (who.int)
  • The aim of this study was to evaluate the prevalence of HBV vaccine escape mutants (VEMs), diagnostic failure mutants (DFMs) and treatment resistance mutants ( ARMs ) among individuals from Buenos Aires, Argentina . (bvsalud.org)
  • Background Fast and reliable detection of Mycobacterium tuberculosis complex (MTBC) and drug resistance is crucial in establishing effective treatment and enforcing timely public health measures. (bmj.com)
  • Insight into treatment of HIV infection from viral dynamics models. (nih.gov)
  • Our definition of resistance therefore does not include cases of intrinsic resistance, sometimes referred to as insensitivity, where a pathogen was never susceptible to treatment. (pnas.org)
  • Someone may be initially infected with a drug-resistant HIV strain or drug resistance may develop during treatment. (labtestsonline.org)
  • CONCLUSION: Three amino acid mutations near but outside of ISDR may associate with interferon treatment resistance of HCV-1b patients in Hong Kong. (biomedsearch.com)
  • Noncompliant patients will usually show elevated viral activity which can lead to increases in treatment failure, transmission, comorbidity, drug resistance, and mortality. (mynewsdesk.com)
  • If proper concentrations of the drugs are not properly maintained in the blood it makes this job a lot easier for the virus and thus will lead to treatment failure sooner. (mynewsdesk.com)
  • Worse still, the drug-resistant mutations that are being found in newly infected people who have never been on treatment are resistant to both first- and second-line drugs. (mynewsdesk.com)
  • In the clinical setting, accurate diagnostic tools have become available to monitor drug resistance in patients who receive treatment with DAAs. (mdpi.com)
  • Antiretroviral treatment may lead to the emergence of HIV drug resistance, which can be transmitted. (hindawi.com)
  • The findings suggest that drugs that are already in clinical trials for inflammatory bowel diseases might be effective in the treatment or prevention of HIV infection. (healthcanal.com)
  • KETEK is indicated for the treatment of community- acquired pneumonia (of mild to moderate severity) due to Streptococcus pneumoniae , (including multi-drug resistant S. pneumoniae [MDRSP 1 ]), Haemophilus influenzae , Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae , for patients 18 years or older. (rxlist.com)
  • Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. (uzh.ch)
  • Drug-resistant pathogens represent one of the major public health and clinical challenges in infectious diseases ( http://www.who.int/drugresistance/en/ ). (prolekare.cz)
  • Microbial Drug Resistance (MDR) is an international, peer-reviewed journal that covers the global spread and threat of multi-drug resistant clones of major pathogens that are widely documented in hospitals and the scientific community. (liebertpub.com)
  • This difference in timing means that, relative to drugs, vaccines tend to keep pathogens from ever achieving large population sizes within hosts. (pnas.org)
  • In addition, drugs tend to target pathogens in a single way ( 9 ) whereas vaccines tend to target pathogens in multiple ways by inducing host-specific antibody and/or T cell responses ( 10 ). (pnas.org)
  • Road map for surveillance and monitoring of HIV drug resistance in the Western Pacific region 2014-2018. (who.int)
  • Epidemiological information and blood specimens were collected for HIV-1 VL and HIVDR testing HIVDR was defined by the Stanford HIV drug resistance algorithm. (who.int)
  • HIV drug resistance threshold survey using specimens from voluntary counselling and testing sites in Hanoi, Vietnam. (who.int)
  • Surveillance of transmitted HIV drug resistance using matched plasma and dried blood spot specimens from voluntary counseling and testing sites in Ho Chi Minh City, Vietnam, 2007-2008. (who.int)
  • In 1998, national and population-based services were proposed for the diagnosis of TB and rifampicin resistance directly from smear-positive patient specimens, 8 and these were adopted in the UK and in other countries using LPAs. (bmj.com)
  • Participants will have blood drawn to learn what anti-HIV drugs the patient's virus is resistant to-that is, what drugs are no longer effective against the virus. (clinicaltrials.gov)
  • Transmission of a drug-resistant virus has been observed in most countries where ART is available [ 4 - 10 ]. (prolekare.cz)
  • People carrying resistant strains can pass them along to others, so that HIV resistance could become even more widespread, the researchers note. (stanford.edu)
  • 11 patients (16%) had drug-resistant virus (Figure). (cdc.gov)
  • samples were considered resistant if they resulted in partial or complete resistance to at least one drug. (usp.br)
  • The virus that causes HIV can become resistant to antiretroviral drugs used to treat the infection. (rexhealth.com)
  • This change leads to a mixed population in the infected person's body - some microorganisms that are drug-resistant and some that are drug-sensitive. (labtestsonline.org)
  • These findings will make us rethink the argument that life-saving antiretroviral drugs should be denied to some populations because poor pill-taking behavior might accelerate the creation of resistant mutations of the HIV virus," said the study's lead author, David R. Bangsberg, MD, MPH. (ucsf.edu)
  • But there's a knock-on effect in that these resistant patients begin spreading a strain of HIV to others that drugs can't treat. (mynewsdesk.com)
  • 3. How does dynamics impact viral fitness and how can it be exploited for therapeutic targeting? (grantome.com)
  • These studies have identified a novel mechanism for the development of mutator DNA polymerases and provide further evidence that antipoxviral therapeutic strategies would not readily be undermined by selection for resistance to ANP drugs. (neb.com)
  • The research is believed to be a first of its kind in fighting viral diseases and IBM Watson, along with such experimental breakthroughs, could help further accelerate drug discovery. (ibm.com)
  • High prevalence of drug resistance was observed among MSM. (medscape.com)