The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.
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).
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.
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).
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.
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.
Simultaneous resistance to several structurally and functionally distinct drugs.
Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
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).
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.
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.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Substances that reduce the growth or reproduction of BACTERIA.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
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.
Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template.
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.
MYCOBACTERIUM infections of the lung.
The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.
Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly.
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 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.
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.
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 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.
A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV INFECTIONS and AIDS.
OXAZINES with a fused BENZENE ring.
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.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
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.
The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding.
An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.
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).
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.
Therapy with two or more separate preparations given for a combined effect.
A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.
An HIV protease inhibitor used in a fixed-dose combination with RITONAVIR. It is also an inhibitor of CYTOCHROME P-450 CYP3A.
An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.
A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.
A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.
A class of plasmids that transfer antibiotic resistance from one bacterium to another by conjugation.
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.
Ribonucleic acid that makes up the genetic material of viruses.
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.
A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children.
Inhibitors of the fusion of HIV to host cells, preventing viral entry. This includes compounds that block attachment of HIV ENVELOPE PROTEIN GP120 to CD4 RECEPTORS.
The co-occurrence of pregnancy and an INFECTION. The infection may precede or follow FERTILIZATION.
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.
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
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.
A republic in southern Africa, the southernmost part of Africa. It has three capitals: Pretoria (administrative), Cape Town (legislative), and Bloemfontein (judicial). Officially the Republic of South Africa since 1960, it was called the Union of South Africa 1910-1960.
A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.
Proteins encoded by the POL GENE of the HUMAN IMMUNODEFICIENCY VIRUS.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
Nonsusceptibility of an organism to the action of penicillins.
Compounds which inhibit or antagonize biosynthesis or actions of integrase.
An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Nonsusceptibility of bacteria to the action of TETRACYCLINE which inhibits aminoacyl-tRNA binding to the 30S ribosomal subunit during protein synthesis.
Voluntary cooperation of the patient in taking drugs or medicine as prescribed. This includes timing, dosage, and frequency.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A republic in eastern Africa, south of SUDAN and west of KENYA. Its capital is Kampala.
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.
Elements of limited time intervals, contributing to particular results or situations.
Opportunistic infections found in patients who test positive for human immunodeficiency virus (HIV). The most common include PNEUMOCYSTIS PNEUMONIA, Kaposi's sarcoma, cryptosporidiosis, herpes simplex, toxoplasmosis, cryptococcosis, and infections with Mycobacterium avium complex, Microsporidium, and Cytomegalovirus.
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.
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.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.
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.
Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.
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.
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.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
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)
Inhibitors of HIV INTEGRASE, an enzyme required for integration of viral DNA into cellular DNA.
An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A.
Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.
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)
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.
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.
Development of neutralizing antibodies in individuals who have been exposed to the human immunodeficiency virus (HIV/HTLV-III/LAV).
Defective metabolism leading to fat maldistribution in patients infected with HIV. The etiology appears to be multifactorial and probably involves some combination of infection-induced alterations in metabolism, direct effects of antiretroviral therapy, and patient-related factors.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
Proteins found in any species of bacterium.
The presence of viruses in the blood.
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.
Voluntary cooperation of the patient in following a prescribed regimen.
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.
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.
A cell line derived from cultured tumor cells.
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.
A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that ferments sugar without gas production. Its organisms are intestinal pathogens of man and other primates and cause bacillary dysentery (DYSENTERY, BACILLARY).
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 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.
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.
The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically.
Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
Nonsusceptibility of a microbe to the action of ampicillin, a penicillin derivative that interferes with cell wall synthesis.
All of Africa except Northern Africa (AFRICA, NORTHERN).
Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.
Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.
Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription.
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 action of a drug that may affect the activity, metabolism, or toxicity of another drug.
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.
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.
Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM.
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.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
Six-membered heterocycles containing an oxygen and a nitrogen.
DYSENTERY caused by gram-negative rod-shaped enteric bacteria (ENTEROBACTERIACEAE), most often by the genus SHIGELLA. Shigella dysentery, Shigellosis, is classified into subgroups according to syndrome severity and the infectious species. Group A: SHIGELLA DYSENTERIAE (severest); Group B: SHIGELLA FLEXNERI; Group C: SHIGELLA BOYDII; and Group D: SHIGELLA SONNEI (mildest).
This drug combination has proved to be an effective therapeutic agent with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.
Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
An infant during the first month after birth.
Any infection which a patient contracts in a health-care institution.
A republic in southern Africa east of ZAMBIA and MOZAMBIQUE. Its capital is Lilongwe. It was formerly called Nyasaland.
Six-carbon alicyclic hydrocarbons.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
Diseases of plants.
Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
A republic in southern Africa, east of ZAMBIA and BOTSWANA and west of MOZAMBIQUE. Its capital is Harare. It was formerly called Rhodesia and Southern Rhodesia.
Tests that demonstrate the relative effectiveness of chemotherapeutic agents against specific parasites.
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.
Process of determining and distinguishing species of bacteria or viruses based on antigens they share.
An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
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.
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)
Genotypic differences observed among individuals in a population.
Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.
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.
Countries in the process of change with economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures.
Gel electrophoresis in which the direction of the electric field is changed periodically. This technique is similar to other electrophoretic methods normally used to separate double-stranded DNA molecules ranging in size up to tens of thousands of base-pairs. However, by alternating the electric field direction one is able to separate DNA molecules up to several million base-pairs in length.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
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 species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.
Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.
A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)
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.
The functional hereditary units of BACTERIA.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Involuntary weight loss of greater than 10 percent associated with intermittent or constant fever and chronic diarrhea or fatigue for more than 30 days in the absence of a defined cause other than HIV infection. A constant feature is major muscle wasting with scattered myofiber degeneration. A variety of etiologies, which vary among patients, contributes to this syndrome. (From Harrison's Principles of Internal Medicine, 13th ed, p1611).
The residual portion of BLOOD that is left after removal of BLOOD CELLS by CENTRIFUGATION without prior BLOOD COAGULATION.
Infections in animals with bacteria of the genus SALMONELLA.
Infections with bacteria of the genus SALMONELLA.
Non-susceptibility of a microbe to the action of METHICILLIN, a semi-synthetic penicillin derivative.
One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.
A method where a culturing surface inoculated with microbe is exposed to small disks containing known amounts of a chemical agent resulting in a zone of inhibition (usually in millimeters) of growth of the microbe corresponding to the susceptibility of the strain to the agent.
Bacteria which retain the crystal violet stain when treated by Gram's method.
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.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
A synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA GYRASE.
Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.
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.
A broad-spectrum antimicrobial carboxyfluoroquinoline.
Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method.
A collection of heterogenous conditions resulting from defective LIPID METABOLISM and characterized by ADIPOSE TISSUE atrophy. Often there is redistribution of body fat resulting in peripheral fat wasting and central adiposity. They include generalized, localized, congenital, and acquired lipodystrophy.
Infections with bacteria of the species ESCHERICHIA COLI.
Inflammatory responses of the epithelium of the URINARY TRACT to microbial invasions. They are often bacterial infections with associated BACTERIURIA and PYURIA.
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.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. 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 at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.
Retroviral proteins coded by the pol gene. They are usually synthesized as a protein precursor (POLYPROTEINS) and later cleaved into final products that include reverse transcriptase, endonuclease/integrase, and viral protease. Sometimes they are synthesized as a gag-pol fusion protein (FUSION PROTEINS, GAG-POL). pol is short for polymerase, the enzyme class of reverse transcriptase.
A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and long-term suppression.
Study subjects in COHORT STUDIES whose outcomes are unknown e.g., because they could not or did not wish to attend follow-up visits.(from Dictionary of Epidemiology, 5th ed.)
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.
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.
Infections with bacteria of the genus STAPHYLOCOCCUS.
An antibacterial agent that is a semisynthetic analog of LINCOMYCIN.
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.
The non-profit, non-governmental organization which collects, processes, and distributes data on hospital use. Two programs of the Commission are the Professional Activity Study and the Medical Audit Program.
Drugs whose drug name is not protected by a trademark. They may be manufactured by several companies.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
A subgenus of Salmonella containing several medically important serotypes. The habitat for the majority of strains is warm-blooded animals.
Drugs which have received FDA approval for human testing but have yet to be approved for commercial marketing. This includes drugs used for treatment while they still are undergoing clinical trials (Treatment IND). The main heading includes drugs under investigation in foreign countries.
A technique of bacterial typing which differentiates between bacteria or strains of bacteria by their susceptibility to one or more bacteriophages.
The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.
DNA elements that include the component genes and insertion site for a site-specific recombination system that enables them to capture mobile gene cassettes.
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.
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.
Infections with bacteria of the species STREPTOCOCCUS PNEUMONIAE.
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.
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.
A technique for identifying individuals of a species that is based on the uniqueness of their DNA sequence. Uniqueness is determined by identifying which combination of allelic variations occur in the individual at a statistically relevant number of different loci. In forensic studies, RESTRICTION FRAGMENT LENGTH POLYMORPHISM of multiple, highly polymorphic VNTR LOCI or MICROSATELLITE REPEAT loci are analyzed. The number of loci used for the profile depends on the ALLELE FREQUENCY in the population.
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.
Infections with bacteria of the family ENTEROBACTERIACEAE.
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.
A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.
A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections.
A republic in southern Africa, between NAMIBIA and ZAMBIA. It was formerly called Bechuanaland. Its capital is Gaborone. The Kalahari Desert is in the west and southwest.
Procedures for identifying types and strains of bacteria. The most frequently employed typing systems are BACTERIOPHAGE TYPING and SEROTYPING as well as bacteriocin typing and biotyping.
... it is both less potent and more resistance prone. Tenofovir is a nucleotide analogue and an antiretroviral drug that is also ... Chronic hepatitis B management aims to control viral replication, which is correlated with progression of disease. Seven drugs ... In the United States and Northern Europe, populations at risk are intravenous drug users and individuals who receive multiple ... Characteristic patterns of liver enzyme abnormalities can point to certain causes or stages of hepatitis. Generally, AST and ...
Excluding Antiretroviral Drugs Section 12: Infections Due to DNA Viruses Chapter 187: Herpes Simplex Virus Infections Chapter ... Acute Viral Hepatitis Chapter 333: Toxic and Drug-Induced Hepatitis Chapter 334: Chronic Hepatitis Chapter 335: Alcoholic Liver ... Gene and Cell Based Therapy in Clinical Medicine Chapter 459: The Human Microbiome Part 17: Global Medicine Chapter 460: Global ... Electrical Storm and Incessant VT Section 4: Disorders of the Heart Chapter 252: Heart Failure: Pathophysiology and Diagnosis ...
The multi-drug resistance genes at Exon 26 C3435T, exon 21 G2677T/A, and exon 12 C1236T have been studied to have SNP's that ... in bases of exon 26 for MDR 1 show a correlation between the MDR 1 gene mutations and the ability of the antiretroviral drugs ... Multiple silent mutated genes tend to be more resistant against these inhibitors. Looking at the molecular level, the reason ... a viral view of genetic engineering through de novo gene and genome synthesis". Chemistry & Biology. 16 (3): 337-47. doi: ...
Sometimes, multiple antibiotics are used in case there is resistance to one antibiotic. Antibiotics only work for bacteria and ... diagnostic tools have enabled physicians and researchers to monitor the efficacy of treatment with anti-retroviral drugs. ... Simultaneously, antimicrobial resistance genes within pathogen and plasmid genomes are sequenced and aligned to the ... Some viral infections can also be latent, examples of latent viral infections are any of those from the Herpesviridae family. ...
In addition to gaining insight into mutation patterns, this study highlights the importance of using multiple types of drugs to ... "Predictors of HIV Drug-Resistance Mutations in a Large Antiretroviral-Naive Cohort Initiating Triple Antiretroviral Therapy". ... In the herpes virus, drugs mainly target the viral DNA polymerase. As a result, mutations in the viral DNA polymerase that make ... A resistance mutation is a mutation in a virus gene that allows the virus to become resistant to treatment with a particular ...
Viral recombination produces genetic variation that likely contributes to the evolution of resistance to anti-retroviral ... The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs. In many parts of the world, HIV has ... The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern of co-receptor usage (including CD4-independence) ... The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow ...
... the swapping of viral gene segments among viruses in the same cell, play a role in resistance, especially in influenza. ... Following the HPTN 052 study and PARTNER study, there is significant evidence to demonstrate that antiretroviral drugs inhibit ... but they all share a general pattern: Attachment to a host cell. Release of viral genes and possibly enzymes into the host cell ... with each replication giving another chance for mutations that encode for resistance to occur. Multiple strains of one virus ...
Sometimes, multiple antibiotics are used in case there is resistance to one antibiotic. Antibiotics only work for bacteria and ... diagnostic tools have enabled physicians and researchers to monitor the efficacy of treatment with anti-retroviral drugs. ... Comparison of viral and bacterial infection Characteristic Viral infection Bacterial infection Typical symptoms In general, ... The use of needle exchange programs in areas with a high density of drug users with HIV is an example of the successful ...
Viral recombination produces genetic variation that likely contributes to the evolution of resistance to anti-retroviral ... The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs. In many parts of the world, HIV has ... The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern of co-receptor usage (including CD4-independence) ... "Estimating drug efficacy and viral dynamic parameters: HIV and HCV". Statistics in Medicine. 27 (23): 4647-57. doi:10.1002/sim. ...
The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the ... Combination of several (typically three or four) antiretroviral drugs is known as highly active anti-retroviral therapy (HAART ... Rutherford GW, Sangani PR, Kennedy GE (2003). "Three- or four- versus two-drug antiretroviral maintenance regimens for HIV ... the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an ...
Drugs: Education, Prevention and Policy. 21: 35-42. doi:10.3109/09687637.2013.798264.. CS1 maint: multiple names: authors list ... regularly taking prophylactic antiretroviral drugs, such as Truvada. Post-exposure prophylaxis, started within 72 hours ( ... Drug abuse 17,000 0.7 WorldwideEdit. The leading causes of preventable death worldwide share similar trends to the United ... Garcia, Patricia, Why Silicon Valley's Paid Leave Policies Need to Go Viral, Vogue, culture, opinion, 2015 ...
... regularly taking prophylactic antiretroviral drugs, such as Truvada. Post-exposure prophylaxis, started within 72 hours ( ... CS1 maint: Multiple names: authors list (link). *^ a b c d e f MMWR. Recommendations and Reports : Morbidity and Mortality ... Drug abuse 17,000 0.7 WorldwideEdit. The leading causes of preventable death worldwide share similar trends to the United ... Garcia, Patricia, Why Silicon Valley's Paid Leave Policies Need to Go Viral, Vogue, culture, opinion, 2015 ...
"Researchers identify second gene mutation linked to HIV resistance". Yahoo! News. Retrieved 31 August 2019. "Scientists ... Canadian company Deep Genomics announces that its AI-based drug discovery platform has identified a target and drug candidate ... "Phage therapy: 'Viral cocktail saved my daughter's life'". BBC News. 8 May 2019. Retrieved 9 May 2019. "415 ppm CO2 threshold ... "End to Aids in sight as huge study finds drugs stop HIV transmission". The Guardian. 2 May 2019. Retrieved 3 May 2019. "Gay HIV ...
Resistance to recently developed drugs such as artemisinin has also been reported. The problem of drug resistance in malaria ... while guanosine analogs inhibit viral DNA polymerase. Resistance to antivirals is thus acquired through mutations in the genes ... Ton Q, Frenkel L (March 2013). "HIV drug resistance in mothers and infants following use of antiretrovirals to prevent mother- ... There are multiple national and international monitoring programs for drug-resistant threats, including methicillin-resistant ...
The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the ... Combination of several (typically three or four) antiretroviral drugs is known as highly active anti-retroviral therapy (HAART ... Rutherford, G. W.; Sangani, P. R.; Kennedy, G. E. (2003). "Three- or four- versus two-drug antiretroviral maintenance regimens ... the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an ...
These drugs are short sequences of RNA that attach to mRNA and stop a particular gene from producing the protein for which it ... Sahin U, Karikó K, Türeci Ö (October 2014). "mRNA-based therapeutics--developing a new class of drugs". Nature Reviews. Drug ... With more than 400 miRNA identified in humans, discerning their target gene for repression is the first challenge. Multiple ... Moreover, unlike plasmids and viral vectors, mRNAs do not integrate into the genome and therefore do not have the risk of ...
AIDS Reviews 2005;7:67-83 Antiretroviral Drug Studies in Nonhuman Primates: a Valid Animal Model for Innovative Drug Efficacy ... coli also have been very useful for the study of gene structure and gene regulation (e.g. phages Lambda and T4). However, it is ... For instance, behavioral analogues of anxiety or pain in laboratory animals can be used to screen and test new drugs for the ... The roundworm Caenorhabditis elegans is studied because it has very defined development patterns involving fixed numbers of ...
Surveillance of transmitted drug resistance to track transmission of viral strains already resistant to ART is also critical. ... Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Sreeram V Ramagopalan, David A Dyment, M Zameel Cader ... HIV-1 drug resistance has the potential to seriously compromise the effectiveness and impact of antiretroviral therapy (ART). ... The method uses free open source software for the interpretation of drug resistance patterns and the generation of individual ...
Surveillance of transmitted drug resistance to track transmission of viral strains already resistant to ART is also critical. ... Analysis of HIV-1 protease gene reveals frequent multiple infections followed by recombination among drug treated individuals ... HIV-1 drug resistance has the potential to seriously compromise the effectiveness and impact of antiretroviral therapy (ART). ... Although a number of anti HIV drugs have been approved, there are still problems with toxicity and drug resistance. This ...
Antiretroviral treatment may lead to the emergence of HIV drug resistance, which can be transmitted. HIV primary drug ... gene (1-268 codons) was genotyped. The sequences were analyzed using the Calibrated Population Resistance (CPR) tool of ... NNRTI drug resistance. Surveillance for primary drug resistance (PDR) needs to be integrated into next generation of HIV ... Stanford University HIV drug resistance (DR) database to identify drug resistance.,i, Results,/i,. Among 37 isolates studied, 6 ...
... by which current antiretroviral drugs exert their remarkable effect on HIV disease despite widespread drug resistance (7, 9). ... Analysis of phenotypic resistance is now frequently performed by cloning the relevant genes into viral constructs to be ... multiple mutations of the protease gene are required for development of significant resistance to the antiproteases. Combining ... In most instances, analysis of mutation patterns well exceeds our current ability to interpret them (13): mutation to one ...
... and may lead to increased viral load and possible resistance to CRIXIVAN or cross resistance to other antiretroviral drugs.. ... Table 7: Drug Interactions With Crixivan: Contraindicated Drugs Drug Class. Drugs Within Class That Are Contraindicated With ... Resistance was mediated by the co-expression of multiple and variable substitutions at these positions. No single substitution ... the extent and spectrum of cross-resistance varied with the specific mutational patterns observed. In general, the degree of ...
... and dida-nosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene ... Multiple drug rescue therapy for HIV-infected individuals with prior virologic failure to multiple regimens. AIDS 15: 61-69. ... The mean number of viral mutations at the principal codons of PR and RT genes is presented in Fig. 2, according to number of ... It is interesting to note that, many of regimens in use and on virological failure included ARV drugs mostly represent the ...
... with mixed strains of drug-susceptible and multidrug-resistant tuberculosis was presumed to have acquired drug resistance ... We started the patient on antiretroviral drugs after initiating isoniazid, rifampin, ethambutol, and pyrazinamide. Phenotypic ... A person may be initially infected with ,1 M. tuberculosis strain with different patterns of drug resistance (1-4). We present ... Both isolates had mutations in the embB gene Leu355Leu (silent) and Glu378Ala (reported as unlikely to cause resistance alone ...
Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations; two arguments for viral load ... A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type 1 confers resistance to multiple ... Novel drug resistance pattern associated with the mutations K70G and M184V in human immunodeficiency virus type 1 reverse ... M184V/I are selected by 3TC/FTC and reduce susceptibility to these drugs ,100-fold. They are also selected by and cause low- ...
Does the addition of resistance levels to antiretroviral drugs, the length of RT and PR sequences, similarity of the RT and PR ... Methods for Computational Gene Prediction. Inferring the correct destinations and splicing styles of genes in DNA is a tricky ... Applying genomic and proteomic microarray technology in drug discovery. *Chirality and Life: A Short Introduction to the Early ... Bouillet trained with information about mutations in the viral genome accurately predict the patients response to therapies? ...
Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to for more ... Mobile Apps. The easiest way to lookup drug information, identify pills, check interactions and set up your own ... maximum viral suppression below the limits of detection with antiretroviral therapy (ART), modification of therapy (if needed ... If intolerance or toxicity develops and virus is not resistant to multiple protease inhibitors: May decrease dose to: ...
Modeling drug resistance in metastatic cancers. Molecularly targeted cancer drugs are often designed to inhibit the action of ... multiple times each day. The transcript levels of 43% of coding genes and 32% of the noncoding genes followed a circadian ... Antiretroviral therapies (ART) can reduce HIV transmission by reducing the number of viral particles in the bloodstream of ... A patchwork pattern of hopane contamination spanning an area of 3,200 km2 likely originated from the Macondo Well and may ...
... which is used to test for resistance against commonly available drugs, and the more variable env gp41 gene region, which is ... HIV mutagenesis and the evolution of antiretroviral drug resistance. Drug Resist. Updates 5:219-223. [PubMed] ... we could argue that drug-selective pressure had resulted in a pattern of parallel evolution. After exclusion of the codon ... Detecting hypermutations in viral sequences with an emphasis on G→A hypermutation. Bioinformatics 16:400-401. [PubMed] ...
Knowing in advance, the HIV-1 resistance - mutations - pattern for each antiretroviral drug, and also for any HAART or Mega- ... may also be used in couples with both single antiretroviral drugs, or with multiple drugs, or with HAART-x regimens. For ... Each antiretroviral drug, and any HAART-x or Mega-HAART-x regimen, divides the HIV-1 viral population in two: 1. drug-sensitive ... is a compilation of mutations in HIV genes that confer resistance to anti-HIV drugs. Both databases can now be used not only ...
... how is insulin resistance related to type 2 diabetes quiz, diabetes type 1 cure research questions, non genetic model of type 2 ... We cannot forget that along the years, patients have done multiple regimes and combinations of antiretroviral drugs, which ... have cell-autonomous properties due to inherently different progenitor cells that exhibit a different gene expression pattern. ... non-antiretroviral drug-induced toxic effects, opportunistic diseases, and perhaps the HIV infection itself [167].. Risk ...
... the established goal of antiretroviral therapy is to reduce viral load to as low as possible for as long as... ... Use of viral resistance patterns to antiretroviral drugs in optimising selection of drug combinations and sequences. Drugs 1996 ... Pol gene quasispecies of human immunodeficiency virus: mutations associated with drug resistance in virus from patients ... Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving ...
Tags: AIDS, Antiretroviral, CD4, Cell, Drugs, Gene, Genes, Genome, HIV, HIV drugs, HIV/AIDS, Life science, Medicine, Pathogen, ... in part because such therapies are believed less likely to elicit drug resistance. A detailed understanding of virus-host ... And so, instead of finding important genes one at a time, you can all at once identify multiple, distinct networks of genes ... Most current drugs against viral infections target the virus itself. But scientists are interested in developing therapies that ...
... emergence of drug resistance mutations is also associated with recombination events that impart resistance to multiple viral ... Emerging drug targets for antiretroviral therapy. Drugs 65:1747-1766. [PubMed]. 44. Richman, D. D. 2001. HIV chemotherapy. ... We isolated viral RNA, synthesized cDNA, and amplified env genes from the selected samples. Due to the variable nature of the ... Similar branching patterns were observed for patients 3501 and 3502, in both cases suggesting that ENF resistance arose ...
Determine the regional and global patterns of resistance to antiretroviral therapies and its impact on long-term antiretroviral ... and to determine the most promising drug candidates. Viral drug resistance remains a major obstacle to effective, long-term ... Evaluate the efficacy of drugs and drug combinations for treating HIV infection and HIV-associated illnesses in infants, ... and mechanism of action of viral genes and proteins; and studies of how the immune system responds to the virus. Knowledge ...
... and predicted expected drug activity for each of 16 antiretroviral drugs. Experts were also asked to make treatment ... Variation in the ATP-binding cassette, subfamily B, member 1 transporter (ABCB1) (multidrug-resistance gene 1) gene has been ... log of baseline HIV viral load, log of minimum post-HAART HIV viral load, and post-HAART log unit reduction in HIV viral load) ... Gene expression patterns vary in clonal cell cultures from Rett syndrome females with eight different MECP2 mutations. BMC ...
HIV drug resistance in adults receiving early versus delayed antiretroviral therapy: HPTN 052External. Palumbo PJ, Fogel JM, ... risk factors and multiple cause-of-death mortality data to estimate the number of deaths that fit the typical pattern for ... The main factor associated with reduced drug resistance with early ART was lower baseline viral load. ... Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and ...
... of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment ... Four open reading frames (ORF) which are called S-gene, C-gene, X-gene and P-gene were identified within the HBV genome. ... number of new antiretroviral drugs and baseline viral load. There was no statistical difference between heterozygous patients ... and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic ...
... patients may respond to antiviral drug treatment.The patients have been treated with antiviral drugs and monitored for viral ... We applied gene amplification techniques in vivo to asses antiretroviral activity of combination therapy. Five HIV-infected ... HIV-1 genotypic resistance patterns predict response to saquinavir-ritonavir therapy in patients in whom previous protease ... Multiple IFN response genes, particularly MX2 in naive B cells and CD163 in CD14+ CD16+ monocytes, were up-regulated in a cell- ...
Drug resistance patterns following pharmacy stock shortage in Nigerian Antiretroviral Treatment Program. AIDS Res Ther. 2017 ... Viral Diversity and Diversification of Major Non-Structural Genes vif, vpr, vpu, tatexon 1 and rev exon 1 during Primary HIV-1 ... Chigwedere, P., Seage, G.R. III, Lee, T.H., and Essex, M. Efficacy of Antiretroviral Drugs in Reducing Mother to Child ... Transmission of Single and Multiple Viral Variants in Primary HIV-1 Subtype C Infection. PLoS One. 2011 Feb 9 ...
... genotype tests and phenotype tests as well as nomenclature of resistance. ... Find in-depth information about two types of hiv resistance testings - ... For other drugs such as AZT, ABC, TDF and most PIs, high-grade resistance requires the serial accumulation of multiple ... Phenotypic assays measure the IC50 of the drug against the virus in vitro. Although, the sensitivity patterns of the virus ...
Antiretroviral drug resistance in non-subtype B HIV-1, HIV-2 and SIV. Antivir Ther. 2004 Feb. 9(1):3-12. [Medline]. ... sex with an injection drug user, MSM, or HIV-infected partner, multiple sexual partners, exchange of sex for money or drugs, ... and genes that encode for accessory proteins (vpu, vpr, vif, and nef) that are important in viral replication and interaction ... The diagnosis can be based on interpretation of the Western blot pattern or detection of the proviral DNA or RNA. [56] Most ...
Primary HIV drug resistance is often observed in newly infected patients. How should clinicians approach management? Dr. Shafer ... decreased in vivo T-cell activation independent of changes in viral replication among patients discontinuing antiretroviral ... Pillay D. Current patterns in the epidemiology of primary HIV drug resistance in North America and Europe. Antivir Ther. 2004;9 ... Multiple studies have reported that T215 revertants are among the most common changes observed in chronically infected newly ...
Antiretroviral drug resistance mutations K103N and E138A were also detected, indicating possible transmission of anti- ... HIV-1 gag p24, pol p10 and p66/p51, pol p31 and env gp41 gene fragments from 43 participants were amplified and sequenced. ... Phylogenetic analysis was inferred using the Maximum Likelihood methods in MEGA version 6. HIV-1 antiretroviral drug resistance ... as well as establish the occurrence and extent of transmitted antiretroviral drug resistance mutations. ...
Viral resistance to currently approved anti-HIV drugs is a significant issue in the clinical management of HIV today. Many ... Gene therapy Clinical Trials Worldwide 2015). There are to date two commercially available approved gene therapy drugs-- ... Chang et al., "A novel class of anti-HIV agents with multiple copies of enfuvirtide enhances inhibition of viral replication ... Research suggests, however, that T20 may be unaffected by resistance to any of the currently approved antiretroviral classes (U ...
von Wyl V, Yerly S, Burgisser P, et al.. Long-term trends of HIV type 1 drug resistance prevalence among antiretroviral ... A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type 1 confers resistance to multiple ... Cases-Gonzalez CE, Franco S, Martinez MA, et al.. Mutational patterns associated with the 69 insertion complex in multi-drug- ... Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human ...
2011). In vivo patterns of resistance to the HIV attachment inhibitor BMS-488043. Antimicrob Agents Ch 55, 729-737.Google ... 2006). Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for ... 1999). HIV-1 drug resistance in newly infected individuals. Jama 282, 1135-1141.Google Scholar ... and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human ...
  • This method enables the identification of sequence mutations, copy number alterations, and select structural rearrangements involving all targeted genes. (
  • Cases of multiple infections may be associated with HIV-1 genetic diversity through recombination allowing for the generation of viruses showing a combination of resistance mutations. (
  • 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. (
  • 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 ]. (
  • When resistant mutations emerge because of drug selective pressure in individuals receiving antiretroviral therapy it is known as acquired resistance. (
  • Although a single mutation of the reverse transcriptase gene might confer a high degree of resistance to some drugs (for example, 3TC and nevirapine), multiple mutations of the protease gene are required for development of significant resistance to the antiproteases. (
  • Viral resistance was correlated with the accumulation of mutations that resulted in the expression of amino acid substitutions in the viral protease. (
  • 3000 nM, and the viruses carried 2 to 10 mutations in the protease gene relative to baseline. (
  • Asp516Gln517Glu) and inhA (C-15T), but the subsequently tested pretreatment sputum isolate was confirmed negative for mutations in the resistance-determining regions of rpoB (rifampin), katG and inhA (isoniazid), and pncA (pyrazinamide). (
  • Both isolates had mutations in the embB gene Leu355Leu (silent) and Glu378Ala (reported as unlikely to cause resistance alone and, more commonly, a marker of Indo-Oceanic strain lineage) ( 6 ). (
  • The table lists the most common clinically significant NRTI-resistance mutations. (
  • Mutations in plain text contribute to reduced susceptibility in combination with other NRTI-resistance mutations. (
  • Bouillet trained with information about mutations in the viral genome accurately predict the patients' response to therapies? (
  • Using a mathematical approach to examine the genetic heterogeneity of cancer cells, Ivana Bozic and Martin Nowak (pp. 15964-15968 ) present a theory that describes the full spectrum of resistance mutations present in a metastatic lesion prior to treatment. (
  • This could be attributed to parallel evolution of drug resistance mutations resulting in the incorrect clustering of multidrug-resistant virus. (
  • Understanding how intrahost evolution translates into HIV evolution at the population level is a key factor in determining how drug resistance and immune escape mutations might spread. (
  • Also, each anti HIV-1 therapeutic-vaccine (Vaccine-x) is made of short HIV-1 - DNA - sequences which contain the point-mutations (resistance-mutations-pattern) that would be induced into HIV-1's genome by the corresponding, following, to come, HAART regimen (HAART-x). (
  • HIV-1- strains that are resistant to an antiretroviral drug present multiple " point-mutations" (PM), which act in synergy to confer the resistant phenotype to that drug, and we may define these "point-mutations" as resistance-mutations-loci (RML) or resistance-mutations-sites (RMS), whereas their ensemble may be termed as resistance-mutations-pattern (RMP). (
  • Paradoxically, and luckily at the same time, point-mutations (PM) that confer drug - resistance, and consequently the whole resistance-mutations-pattern (RMP-x) of a (HAART-x) regimen offers us the complete biochemical information, for the development of very specific and powerfull vaccine(s) and therapeutic vaccines (Vaccine-x) against HIV-1. (
  • The clinical use of the human immunodeficiency virus (HIV) fusion inhibitor enfuvirtide (ENF) can select for drug-resistant HIV-1 strains bearing mutations in the HR1 region of the viral envelope (Env) protein. (
  • Coreceptor usage patterns of the Envs isolated from two patients underwent homogenization following ENF therapy, whereas in the other three patients, recombination appeared to allow the introduction of a single HR1 sequence with ENF resistance mutations into phenotypically distinct Env proteins. (
  • Studies done on Indian population indicate that prevalence of HIV resistance mutations is around 9.6% in treatment naïve population and up to 81-96% in treatment experienced patients with virological failure. (
  • For other drugs such as AZT, ABC, TDF and most PIs, high-grade resistance requires the serial accumulation of multiple mutations and is thus slower to emerge. (
  • An HIV-1 genotype resistance assay revealed the reverse transcriptase (RT) mutations M41M/L and T215C. (
  • Note: Statistically significant increased rates of virologic failure occurred in patients with baseline RT inhibitor-resistance mutations. (
  • Hardly any studies of HIV diversity have been undertaken in Mpumalanga Province, and this study sought to investigate the HIV-1 diversity in this province, as well as establish the occurrence and extent of transmitted antiretroviral drug resistance mutations. (
  • HIV-1 antiretroviral drug resistance mutations were determined using the Stanford database. (
  • Antiretroviral drug resistance mutations K103N and E138A were also detected, indicating possible transmission of anti-retroviral drug resistance mutations. (
  • Logistic regressions adjusted for the antiretroviral treatment history were performed to analyze the association of the polymorphic mutations with MNR. (
  • Besides antiretroviral therapy, polymorphic mutations may contribute to the emergence of specific MNR mutations. (
  • In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. (
  • Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. (
  • Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. (
  • We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone. (
  • They could not have major reverse transcriptase or protease resistance mutations. (
  • Drug-resistant strains of HIV-1 harbor mutations that can negatively impact viral fitness, but these viruses gain a replicative advantage in the presence of drug and can be associated with treatment failure and clinical progression [ 5 , 6 ]. (
  • The extent to which HIV-specific immune responses suppress the emergence of drug-resistant strains is not well understood, but may be influenced by immune recognition of epitopes containing key resistance mutations. (
  • Resistant isolates have been characterized with regard to cross resistance to other drugs, enzymatic activity of the target protein, mutations in the target gene and protein, and the relationship of these mutations to the x-ray crystallographic structure of the enzyme. (
  • Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). (
  • Detection of mutations associated with zidovudine resistance in human immunodeficiency virus utilizing the polymerase chain reaction. (
  • Nevirapine resistance mutations of HIV-1 selected during therapy. (
  • Dr. Kozal is a translational researcher who has focused his research career on three areas: 1) investigating the genetic determinants of HIV and HCV drug resistance, 2) the development of new molecular methods to detect viral mutations, and 3) HIV and HCV clinical trials involving new drugs and diagnostic technology. (
  • Detection of drug resistance mutations in the human immunodeficiency virus type 1 (HIV-1) pol gene: differences in semen and blood HIV-1 RNA and proviral DNA. (
  • Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. (
  • Shafer RW, Kozal MJ, Winters MA, Iversen AK, Katzenstein DA, Ragni MV, Meyer WA, Gupta P, Rasheed S, Coombs R. Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. (
  • The absence of detectable resistance to a drug does not ensure that use of the drug will be successful, as mutations may not be detected once the drug has been discontinued. (
  • We developed an HIV-1 protease and reverse transcriptase drug resistance genotyping assay applicable to DBS samples and HIV-1 genomes of groups M, N and O. The WHO 2009 list of mutations for surveillance of transmitted drug-resistant HIV strains was used to analyse TDRMs. (
  • We investigated the HIV molecular transmission network, genetic tropisms, and drug resistance mutations in Tianjin. (
  • By identifying common clustering among MSM, we examined the HIV molecular transmission network and transmitted drug resistance mutations to determine the characteristics of the HIV epidemic in Tianjin at the provincial level to guide HIV prevention measures. (
  • Maximum likelihood phylogenetic analysis (using fastDNAmL [14]) was performed on all pol sequences to determine if viruses that harbored drug-resistance-associated mutations clustered together, thereby identifying a potential transmission network of the drug-resistant virus. (
  • A second was concordant identification of codons at sites identified with resistance mutations in the sample, although scoring of these criteria is still undetermined from this study. (
  • Genotypic changes in the YMDD motif (reverse transcriptase [rt] mutations rtM204V/I) conferred resistance to lamivudine as well as reducing the in vitro replication efficiency of HBV. (
  • In vitro analyses have confirmed and characterized the role of the major HBV polymerase mutations in lamivudine resistance. (
  • Cell culture and enzyme assays have revealed that rtM204V/I mutations are sufficient to confer resistance to lamivudine and structurally related inhibitors (reviewed in reference 13 ). (
  • In addition to conferring drug resistance, single rtM204V/I mutations also reduce the replication of HBV in vitro ( 22 , 27 , 28 ). (
  • The resting memory CD4 + T cells can live for long periods of time, contribute to low-level persistent viremia during cART and viral rebound after treatment interruption, and produce viral variants with escape mutations (Chun et al . (
  • Their genotype and drug-resistance mutations were identified using bioinformatics tools. (
  • There are two ways for testing: Phenotyping, where the resistance factor is measured directly by experiments and genotyping, where important regions of the genome are scanned for mutations. (
  • artificial intelligence, drug combination, combination therapy, machine learning, genomic profile Introduction It is becoming increasingly clear that targeted combination therapy is the treatment of choice in many complex human diseases, particularly those resulting from biological dysfunction driven by alterations/mutations in several genes or/and gene networks as is usually the case in cancer [1]. (
  • Absence of HIV-1 drug resistance mutations supports the use of dolutegravir in Uganda. (
  • The present study investigated the prevalence of HIV-1 multiple infections in a population composed by 47 patients under HAART failure and enrolled at the National DST/AIDS, Program, Ministry of Health, Brazil.Detection of multiple infections was done using a previously published RFLP assay for the HIV-1 protease gene, which is able of distinguishing between infections caused by a single or multiple HIV-1 subtypes. (
  • This is the first study that reports the prevalence of multiple infections and intersubtype recombinants in a population undergoing HAART in Brazil. (
  • These concepts provided the impetus to treat a large proportion of HIV-infected individuals with a combination of antiretroviral drugs [highly active antiretroviral therapy (HAART)], resulting in a dramatic reduction in AIDS-related morbidity and mortality ( 2 ). (
  • The factors leading to this type of failure are straightforward: poor adherence to HAART, prior exposure to antiretroviral drugs in mono- or bi-therapy, the sequential addition of drugs to a failing regimen, and counteractive interactions among the drugs used ( 5 )-nothing new for those who witnessed the early days of antituberculosis chemotherapy in the 1950s and 1960s. (
  • Treating HIV-1-infected patients with highly active antiretroviral therapy (HAART) has led to a remarkable reduction in HIV-related morbidity and mortality ( 28 ). (
  • Multidrug resistant HIV-1 strains arise in patients treated with HAART or Mega-HAART regimens, either through direct mutation or through recombination of variants that are resistant to single drugs. (
  • Conduct studies on the effects of highly active antiretroviral therapy (HAART) on virologic and immunologic markers of disease progression and long-term effects in diverse populations, including post-exposure and high-risk cohorts. (
  • ABSTRACT Aims To study sexual risk and injecting behaviour among HIV-infected drug users (DU) receiving highly active antiretroviral therapy (HAART). (
  • Relative to homosexual men, DU had a similar initial therapeutic response, but DU started HAART at lower CD4 cell counts and higher viral load levels. (
  • This suggests that selection of potential HAART starters is based on limited drug use. (
  • The DHHS has excellent guidelines for initial highly active antiretroviral therapy (HAART). (
  • However, progression from HIV infection to AIDS and HIV-related mortality can be reduced effectively by several years of treatment with highly active antiretroviral therapy (HAART). (
  • The population of HIV replicating within a host consists of independently evolving and interacting sub-populations, as demonstrated by the various degrees of phylogenetic compartmentalization seen across and within anatomical compartments and various rates of decay in viral load during HAART therapy [ 1 , 2 ]. (
  • Treatment interruption when HAART is associated with a detectable viral load, sometimes called 'treatment failure. (
  • The study protocol included restarting HAART if, during the STI, the viral load increased to greater than 50,000 copies per milliliter once or to greater than 5,000 copies per milliliter for three consecutive weeks. (
  • The successful use of highly active antiretroviral therapy (HAART) can dramatically suppress human immunodeficiency virus (HIV)-1 viral replication and effect significant immune reconstitution. (
  • The past couple of years have seen a marked increase in the use of combinations of highly active antiretroviral therapy (HAART) that contain two protease inhibitors (PIs), usually ritonavir (Norvir) plus another PI. (
  • Viral breakthrough also has been especially common in those with pre-HAART treatment histories that triggered the formation of drug-resistant HIV and limited the effectiveness of supporting nucleoside analogs ( NRTIs ) in indinavir-containing regimens. (
  • Based on the data there was a steep increase of multiple infections after the introduction of the combined antiretroviral therapy in Brazil. (
  • The current study provides detailed protocols utilized to amplify the complete HIV-1 gp120 and nef genes from single copies of expressed or integrated HIV present in fresh-frozen autopsy tissues of patients who died while on combined antiretroviral therapy (cART) with no detectable plasma viral load (pVL) at death (Lamers et al . (
  • The reverse transcriptase region of HIV-1 pol gene (1-268 codons) was genotyped. (
  • Among 37 isolates studied, 6 (16.2%) samples showed primary drug resistance (PDR) against reverse transcriptase (RT) inhibitor. (
  • Injecting drug user (IDU) has showed resistance to either nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) or nonnucleotide reverse transcriptase inhibitors (NNRTI). (
  • This involves the nucleotide sequencing of the relevant HIV genes , from which an amino acid sequence of the reverse transcriptase and protease enzymes is predicted. (
  • The number refers to the position of that particular amino acid within either the protease gene or the reverse transcriptase gene. (
  • Thus, M184V signifies that the usual amino acid in drug sensitive viruses, methionine (M), at the 184th amino acid of the reverse transcriptase protein has been replaced by a V (valine), which leads to high level resistance to Lamivudine. (
  • The pol gene encodes the enzymes reverse transcriptase, integrase, and protease. (
  • The drugs for treatment of HIV infection are categorized as nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs) and non- nucleoside reverse transcriptase inhibitors (NNRTIs). (
  • To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT) inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. (
  • While the majority of researchers have advocated a view that this syndrome is predominantly a drug-related side effect mediated by contributions from both the nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI) classes of antiretroviral medications, some studies, such as the recent HIV Outpatient Study (HOPS), have demonstrated no evidence of antiretroviral class-specific effects. (
  • I shall briefly summarize the status of the in vitro data with reverse transcriptase inhibitors before concentrating upon more recent developments in the field relating to resistance to protease inhibitors, the interrelationships of pathogenesis and drug resistance, and the clinical significance of drug resistance. (
  • Viral resistance to human immunodeficiency virus type 1-specific pyridinone reverse transcriptase inhibitors. (
  • Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine. (
  • Functional Analysis of HIV-1 Reverse Transcriptase Amino Acids Involved in Resistance to Multiple Nonnucleoside Inhibitors. (
  • Currently marketed HIV-1 drugs are dominated by either nucleoside reverse transcriptase inhibitors or peptidomimetic protease inhibitors. (
  • Genotyping of the human immunodeficiency virus type 1 (HIV-1) protease (PR) and reverse transcriptase (RT) genes by population sequencing to assess antiretroviral resistance is a standard diagnostic assay to aid the clinical management of HIV-infected individuals ( 3 ). (
  • 6-9 After viral entry, HIV-1 reverse transcriptase converts its single-stranded RNA into double-stranded DNA (dsDNA), at which time integrase assembles in a stable complex with viral DNA-the pre-integration complex-and is chaperoned into the nucleus. (
  • This demonstrates a need to identify new compounds that can inhibit infection by the common drug resistant HIV-1 strains with minimal toxicity. (
  • The level of primary drug resistance was studied among 37 recently infected HIV cases identified by Limiting antigen (Lag) avidity assay based on modified Recent Infection Testing Algorithm (RITA). (
  • 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 ]. (
  • A patient who had initial infection with mixed strains of drug-susceptible and multidrug-resistant tuberculosis was presumed to have acquired drug resistance before confirmation that sequential strains were genotypically distinct. (
  • Multidrug-resistant (MDR) tuberculosis (TB), defined as infection with Mycobacterium tuberculosis that is resistant to isoniazid and rifampin, can be transmitted and manifest as a primary infection without a patient having received those medications or can be acquired by the patient during drug therapy. (
  • Here we have characterized an HIV-1 transmission chain consisting of nine infected patients, almost all of whom were treated with antiviral drugs at later stages of infection. (
  • Lipodystrophy: The Metabolic Link of HIV Infection with Insulin-Resistance SyndromePaula Freitas1, Davide Carvalho1, Selma Souto1, Antonio Sarmento1 and Jose Luis Medina1[1] Department of Endocrinology, Centro Hospitalar Sao Joao and University of Porto Medical School, Porto, Portugal1. (
  • Viral dynamics in human immunodeficiency virus type 1 infection. (
  • The sustained suppression of circulating HIV-1 in indinavir-treated patients is a consequence of the complete prevention of new viral infection cycles. (
  • In a paper published in Molecular Cell , the team describes a map of the genes controlling HIV infection in human cells, which they built by assessing more than 63,000 combinations of human genes associated with HIV infection. (
  • Studying the impact of gene disruptions in pairs rather than one by one yields important information on how genes work together to mediate virus infection, highlighting processes we can target with drugs to inhibit infection. (
  • The most tricky part was to implement a sophisticated data acquisition and scoring system, which allowed them to measure HIV infection accurately across hundreds of thousands of samples, and compare the effect of pairwise and single-gene disruptions. (
  • Current therapies for the treatment of human immunodeficiency virus type 1 (HIV-1) infection employ potent antiretroviral drugs that target reverse transcription of the viral RNA genome (RT inhibitors) and virion maturation (protease inhibitors) ( 44 ). (
  • Understand the changing pattern of HIV infection throughout the world, and the impact of therapeutic, vaccine, and other prevention-based interventions on survival and clinical outcome. (
  • High Rates of Occult Hepatitis B Virus Infection in HIV-Positive Individuals Initiating Antiretroviral Therapy in Botswana. (
  • HIV infection can be diagnosed based on detection of antibodies that are directed against the proteins encoded by the 3 major genes, the detection of the p24 antigen, the viral nucleic acid, and, finally, by means of culturing the virus. (
  • He is an Associate Professor in the Division of Infectious Diseases at Stanford University Medical Center and an expert on the management of HIV infection, with a particular focus on antiretroviral drug resistance mechanisms and testing. (
  • The standard of care in Human Immunodeficiency Virus (HIV) infection is the use of a triple drug antiretroviral regimen. (
  • CD4 cell count can be monitored less frequently (every 6-12 months) in children and youth who are adherent to therapy and have CD4 cell count values well above the threshold for opportunistic infection risk, sustained viral suppression, and stable clinical status for more than 2 to 3 years (AII) . (
  • TB is the leading infection cause of death globally, with increasing drug resistance. (
  • These data argue that neutralizing antibody responses account for the extensive variation in the envelope gene that is observed in the early months after primary HIV infection. (
  • RNA interference is an important innate defense mechanism in which the RNA-Inducing Silencing Complex (RISC) degrades the viral mRNA and the cell survives the infection. (
  • QIAGEN's HIV Infection and Host Response PCR arrays can help you study the gene expression involved in this pathological process. (
  • This study demonstrates a higher rate of HIV drug resistance among antiretroviral-naive individuals with unknown duration of HIV infection than previously described. (
  • Abstract: In clinical settings, we have found a high rate of human immunodeficiency virus (HIV) drug resistance among antiretroviral-naive patients for whom the duration of infection was unknown. (
  • Most transmitted drug resistance can be detected with standard population-based pol sequencing (genotype testing) for at least 3 years after initial infection [8-10]. (
  • Nine San Diego County HIV clinics participated in this study, and 103 individuals with an unknown duration of infection received standard drug-resistance testing (performed at Monogram Biosciences [San Francisco, CA]). Twenty-six (25%) of these individuals harbored HIV strains that were resistant to at least 1 class of antiretroviral agents. (
  • The acute form of hepatitis, generally caused by viral infection, is characterized by constitutional symptoms that are typically self-limiting. (
  • Therapy of chronic hepatitis B virus (HBV) infection with the polymerase inhibitor lamivudine frequently is associated with the emergence of viral resistance. (
  • People with a DNA mutation that reduces their chance of HIV infection may die sooner, according to a study that suggests tinkering with a gene to try to fix one problem may cause others. (
  • 15-18 Inhibiting integrase from performing its essential functions therefore blocks stable integration of HIV-1 DNA into the host genome and prohibits the establishment of viral latency within the host cell, preventing high-level HIV-1 replication and infection of new cells by competent virus. (
  • In addition, the virus experiences different selective pressures at multiple levels: during the course of infection, at transmission, and among individuals. (
  • This dataset substantially increases the availability of HIV-1 sequence data that spans multiple years of untreated infection, in particular for different geographical regions and viral subtypes. (
  • The evolution of antibiotic resistance in opportunistic pathogens such as Streptococcus pneumoniae, Escherichia coli or Staphylococcus aureus is a major public health problem, as infection with resistant strains leads to prolonged hospital stay and increased risk of death. (
  • The past 2 years have witnessed remarkable advances in the development of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection, as well as measurement of HIV plasma RNA (viral load) to guide the use of antiretroviral drugs. (
  • The first article, Report of the NIH Panel To Define Principles of Therapy of HIV Infection, provides the basis for the use of antiretroviral drugs, and the second article, Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, provides specific recommendations regarding when to start, how to monitor, and when to change therapy, as well as specific combinations of drugs that should be considered. (
  • However, as antiretroviral therapy for HIV infection has become increasingly effective, it has also become increasingly complex. (
  • 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 ]. (
  • Achieving this with the currently available antiretroviral agents involves appropriate selection of components of combination regimens to obtain an optimal antiviral response. (
  • Viral drug resistance remains a major obstacle to effective, long-term therapy, and new therapeutic regimens are necessary to minimize viral replication and burden in the body. (
  • Emulating a target trial of antiretroviral therapy regimens started before conception and risk of adverse birth outcomes. (
  • The success of complex antiretroviral regimens is dependent on consistent adherence of patients to the drugs. (
  • HA060 trade name] provides a combination of drugs i.e. lamivudine and zidovudine, that are already established as a backbone of the triple drug regimens. (
  • The lipodystrophy syndrome is distressing to HIV-positive patients on ART and has been linked with both short-term and long-term failure to comply with antiretroviral regimens. (
  • Phenotypic resistance testing should be used (usually in addition to genotypic resistance testing) for patients with known or suspected complex drug resistance mutation patterns, which generally arise after virologic failure of successive ART regimens (BIII) . (
  • choosing new regimens for those failing ARV therapy) ( 4 ) These assays comprise multiple sequential components and require expertise in both the physical performance of the assays and the subjective evaluation of the generated data (Fig. 1 ). (
  • Current cART regimens encompass a variety of drugs that inhibit viral replication in several ways, which allows for the almost complete suppression of viral particles found in the blood and recovery of a healthy CD 4+ T-cell population (CD 4+ ) (Autran et al . (
  • For example, based on gene alterations, it would be not unreasonable for a cancer treatment regimen to require six or more drugs (each targeting a particular genetic alteration), and when one considers the multiple possible dosing regimens, the number of potential combinations rapidly multiplies, achieving numbers as high as 1011 [2]. (
  • Surveillance of transmitted drug resistance to track transmission of viral strains already resistant to ART is also critical. (
  • Here we describe an efficient assay that can be used to rapidly determine the cellular cytotoxicity and efficacy of a compound against WT and mutant viral strains. (
  • As with other antiretroviral drugs, entry inhibitor therapy can select for resistant HIV-1 strains. (
  • Retrospective studies have shown that persons infected with drug-resistant strains have an increased risk for virologic failure when treated with drugs to which their virus was resistant (for an example, see Figure 2 [4] ). (
  • Sub-optimal adherence may reduce the effectiveness of the regimen by allowing viral replication and the emergence of drug resistant strains. (
  • Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful antiretroviral therapy (ART) in HIV-infected patients. (
  • Twenty-six (25%) of these individuals harbored HIV strains that were resistant to at least 1 class of antiretroviral agents. (
  • However, the major drawback to the development and application of NNRTIs is the propensity for rapid emergence of drug resistant strains, both in tissue cell culture and in treated individuals, particularly those subject to monotherapy. (
  • These highly drug-resistant strains are distinguished into 5 major MRSA lineages and are further delineated based on the genetic organization of the staphylococcal chromosomal cassette that harbors the methicillin resistance determinant, mecA ( SCC mec ). (
  • In contrast to these highly drug resistant hospital strains, the Midwestern CA-MRSA strain (referred to as MW2) usually carries less antibiotic resistance determinants and is often sensitive to non-b-lactam agents (ie, clindamycin and aminoglycosides). (
  • It is interesting to note that the cassette that harbors the mecA gene is also capable of trapping drug resistant plasmids and transposons and thereby increasing the drug resistance of these S aureus strains. (
  • Nearly all CA-MRSA strains appear to have the PVL gene, which has served as a genetic marker for identifying CA-MRSA. (
  • APTIVUS, co-administered with ritonavir, is indicated for combination antiretroviral treatment of HIV -1 infected patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor ( PI ). (
  • 1-4 However, despite full access to antiretroviral agents, the emergence of antiretroviral-resistant HIV-1 strains and/or drug toxicities can derail effective treatment. (
  • In the absence of evidence that eradication of HIV from an infected individual is feasible, the established goal of antiretroviral therapy is to reduce viral load to as low as possible for as long as possible. (
  • 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. (
  • Central to its complexity are the phenomenon of HIV quasi-species (the simultaneous presence in a patient of a swarm of viral variants), the extent of cross-resistance among antiviral drugs, the existence in each individual of archival HIV DNA copies representing all viruses that emerged under previous treatment, and the preexistence of resistant variants even without prior exposure to the drug ( 11 ). (
  • Third, transmitted drug resistance often persists for 3 or more years, allaying concerns that transmitted resistant variants would be rapidly overgrown by wild-type variants and therefore no longer detectable if transmission had occurred more than several months earlier. (
  • These results support the concept that anti-viral immunity acts synergistically with ART to augment drug efficacy by suppressing replication of viral variants with reduced drug sensitivity. (
  • Whether these responses control replication of drug-resistant HIV-1 in vivo , and whether they can be induced in HIV-infected patients as a protective measure against the emergence of drug-resistant viral variants is unknown. (
  • As a result, mixed nucleotides (mixtures) at individual nucleotide positions may be evident in sequence analysis and may indicate viral variants of increasing or declining resistance. (
  • Disentangling how these evolutionary forces shape the evolution of the virus at the population scale is important for understanding pathogenesis, how drug- and immune-escape variants are likely to spread in populations, and the development of preventive vaccines. (
  • Furthermore, when used appropriately, combinations of newly available, potent antiviral therapies can effect prolonged suppression of detectable levels of HIV replication and circumvent the inherent tendency of HIV to generate drug-resistant viral variants. (
  • Nonetheless, regardless of subtype, K65R is the most common NRTI-associated resistance mutation other than M184V to develop in patients receiving a TDF-containing regimen. (
  • Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to for more information) when necessary. (
  • HIV-1 recombination and mutation ( 1 , 2 , 3 , 4 , 5 , 6 ), including "resistance-mutation", are important mechanisms by which HIV-1 evades drug or immune pressures. (
  • Drugs for which the virus requires only one mutation to develop high level resistance (such as Lamivudine and Nevirapine) will in fact generate very rapid resistance when used as monotherapy. (
  • Eight sequences clustered with at least one other shared the same drug resistance mutation (DRM). (
  • K103N was the most common drug-resistance-associated mutation, appearing in sequences obtained from 12 patients. (
  • A second mutation, rtL180M, was previously reported to partially restore replication fitness as well as to augment drug resistance in vitro. (
  • Here we report the functional characterization of a third polymerase mutation (rtV173L) associated with resistance to lamivudine and famciclovir. (
  • BACKGROUND The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses. (
  • The use of effective antiretroviral therapy (ART) has resulted in tremendous improvements in morbidity and mortality in HIV-positive patients. (
  • Although advances in combination antiretroviral therapy (ART) have greatly reduced morbidity and mortality associated with HIV, the pipeline for development of novel drug mechanisms and new agents in the existing drug classes remains full. (
  • Partial pol and env gp41 regions of the HIV genome were directly sequenced from plasma viral RNA for at least one sample from each patient. (
  • It would be an overwhelming effort to test all combinations of the over 20,000 protein-coding genes in the human genome. (
  • The highly replicative nature of HCV, coupled with error-prone viral RNA synthesis and considerable genome diversity, pose extraordinary challenges to therapy development. (
  • When you expose the human ES cells to atmospheric oxygen for just a few days, the whole genome goes crazy - there are massive gene expression changes," says Lengner. (
  • This limitation results from the fact that the virus genome is integrated into the host s genome and from the development of drug resistance. (
  • Genetic linkage analysis and genotyping of candidate genes in families with 4 or more affected individuals more heavily loaded for susceptibility genes has not fully explained familial disease clustering. (
  • Isolates of HIV-1 with reduced susceptibility to the drug have been recovered from some patients treated with indinavir. (
  • Phenotypic susceptibility tests later confirmed MDR TB: 25% resistance to isoniazid at 1.0 μg/mL and 100% resistance to rifampin at 1.0 μg/mL. (
  • The inability to culture human Pneumocystis , Pneumocystis jirovecii , in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. (
  • Since HIV drug resistance was first recognized, many studies have documented the emergence of isolates with reduced susceptibility under the selective pressure of drug therapy, both in vitro and in vivo . (
  • Phylogenetic analysis was performed with all amino acid residues included and with those residues associated with decreased drug susceptibility removed. (
  • Expression of mecA yields a penicillin binding protein (PBP2a) that reduces the bacterium's susceptibility to all b-lactam drugs. (
  • M184V/I are associated with reduced viral replication in vitro and in vivo ( 31 , 32 , 33 , 34 , 35 , 36 , 37 ). (
  • Finally, we have to learn more about the mechanisms by which current antiretroviral drugs exert their remarkable effect on HIV disease despite widespread drug resistance ( 7 , 9 ). (
  • In particular, the frequent observation of increasing CD4 cell counts in individuals maintaining high viremia levels needs to be explained, because it may yield clues regarding issues such as viral fitness, resetting in the steady state of CD4 cell turnover, and the possible action of protease inhibitors on nonviral targets participating in the mechanisms of CD4 T cell depletion. (
  • 5 Consequently, the need to develop antiretroviral agents with novel mechanisms of action persists for the treatment of both antiretroviral-experienced and antiretroviral-naïve patients. (
  • for anti HIV assays a predetermined amount of either a WT or drug resistant HIV-1 vector that expresses luciferase is added to the cells. (
  • This implies that resistant clones may be present well below detection levels and emerge only when the specific antiretroviral drug is introduced. (
  • In countries where antiretrovirals are widely used, growing concern exists about the transmission of resistant viruses. (
  • However, the choice of drug should also be guided by tolerability profiles and considerations of coverage of the widest range of infected cells, compartmental penetration, pharmacokinetic interactions and, importantly, the ability of an agent or combination to limit future therapeutic options through selection of cross-resistant virus. (
  • We analyzed the properties of multiple Env proteins isolated from five patients who experienced an initial decline in viral load after ENF therapy followed by subsequent rebound due to emergence of ENF-resistant HIV-1. (
  • Despite the potency of these antiretroviral agents, several complications exist that limit their efficacy in the clinic, including viruses resistant to one or more antiviral drugs ( 30 ). (
  • Determine the prevalence of drug-resistant HIV and its relationship to disease. (
  • Although, the sensitivity patterns of the virus tested can be determined, it may not detect minor species of resistant viruses. (
  • Rates of virologic failure among those with wild-type and drug-resistant viruses were higher in the ddI/d4T/efavirenz arm (the ddI/d4T combination is no longer recommended because of its increased toxicity and decreased efficacy). (
  • Although effective, the implementation of such strategy faces great financial, political and social challenges in heavily affected regions such as developing countries where drug resistant viruses have already been found with growing incidence. (
  • Although fewer cases of PCP occur in the industrialized countries, increasing drug-resistant HIV infections, possible drug-resistant PCP, and to the tremendous number of AIDS cases in developing countries make this disease of continued public health importance. (
  • Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV). (
  • Treatment strategies that seek to combine immunotherapeutic intervention as an adjunct to antiretroviral drugs may therefore confer added benefit by controlling replication of HIV-1, and reducing the likelihood of treatment failure due to the emergence of drug-resistant virus, thereby preserving treatment options. (
  • the sensitivity of drug-resistant mutants does not. (
  • A superbug (with mcr-1 gene) resistant to antibiotics now exists on several continents. (
  • Phylogenetic analysis of all sequences with and without amino acid residues associated with drug resistance demonstrated no significant clustering of viral sequences that would indicate a network of transmission of drug-resistant virus (data not shown). (
  • Foscarnet, a drug used in acyclovir resistant herpes zoster, works by interfering with the binding of pyrophosphate to viral DNA polymerase and, thus, preventing viral replication. (
  • This medication is not dependent on viral thymidine kinase, thereby making it the treatment of choice of acyclovir-resistant patients. (
  • In vitro analyses indicated that rtV173L did not alter the sensitivity of wild-type or lamivudine-resistant HBV to lamivudine, penciclovir, or adefovir but instead enhanced viral replication efficiency. (
  • This third goal applies to situation 'III' below, when there is drug-resistant, detectable virus. (
  • Failure has generally been defined in virological terms-the inability to achieve complete suppression of viral replication. (
  • Additionally, the brain is a sanctuary site for the development of drug resistance, because poor antiretroviral drug penetration into the CNS leads to sub-therapeutic drug concentrations and incomplete suppression of viral replication [ 6 ]. (
  • In drug combination studies with the nucleoside analogues zidovudine and didanosine, indinavir showed synergistic activity in cell culture. (
  • Evaluation of human immunodeficiency virus (HIV) type 1 RNA levels in cerebrospinal fluid and viral resistance to zidovudine in children with HIV encephalopathy. (
  • Effect of stage of disease and drug dose on zidovudine susceptibilities of isolates of human immunodeficiency virus. (
  • Didanosine resistance in HIV-infected patients switched from zidovudine to didanosine monotherapy. (
  • Additive or synergistic in vitro inhibition has been reported with double or triple combinations of numerous antiretroviral agents, except for zidovudine-stavudine, which is an antagonistic combination. (
  • The sequences were analyzed using the Calibrated Population Resistance (CPR) tool of Stanford University HIV drug resistance (DR) database to identify drug resistance. (
  • Does the addition of resistance levels to antiretroviral drugs, the length of RT and PR sequences, similarity of the RT and PR to their reference sequences, HIV subtype, and epitope information significantly enhance the accuracy of the classifiers? (
  • Using sequences sampled in the gag and env genes, several tree reconstruction methods were tested for their ability to reconstruct the true transmission history. (
  • A subset of human immunodeficiency virus type 1 long-term non-progressors is characterized by the unique presence of ancestral sequences in the viral population. (
  • Sequences are annotated with clinical data including viral load, CD4 count, antiretroviral status, neurocognitive impairment, and neuropathological diagnosis, all curated from the original publication. (
  • METHODS DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012. (
  • Viral load measurement every 3 to 4 months is generally recommended to monitor ART adherence and disease progression (AIII) . (
  • Here we analyzed a subset of viremic controller patients and demonstrated that similar to the phenomenon observed in patients with a discordant response to antiretroviral therapy (i.e., high CD4 + cell counts with detectable plasma HIV-1 RNA load), reduced viral replicative fitness seems to be linked to slow disease progression in these antiretroviral-naïve individuals. (
  • However, when used in combination, these drugs have a profound effect on viremia and disease progression. (
  • Time to first positive HIV-1 DNA PCR may differ with antiretroviral regimen in infants infected with non-B subtype HIV-1. (
  • A discussion of this issue is timely because primary or transmitted drug resistance has been increasing over the past 5-10 years and drug resistance testing is now recommended for previously untreated persons as well as for persons failing a treatment regimen. (
  • A two-drug combination of dolutegravir and lamivudine - the drugs in the Dovato co-formulation - continued to suppress viral load as well as a standard three-drug regimen in people starting their initial HIV treatment. (
  • The combination also maintained viral suppression in those who switched from a standard regimen. (
  • After initiation of ART, or after a change in ART regimen, children should be evaluated for clinical adverse effects and to support treatment adherence within 1 to 2 weeks, with laboratory testing for toxicity and viral load response recommended at 2 to 4 weeks after treatment initiation (AIII) . (
  • While long-term engraftment of donor cells was not observed, the non-lethal preparative conditioning regimen was able to reduce the viral burden and improved the clinical outcome. (
  • 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. (
  • Although combination antiretroviral therapy can dramatically suppress HIV replication for an extended period in some patients (Carpenter et al. (
  • In patients with HIV, genotypic resistance testing is preferred. (
  • Plasma HIV-1 RNA levels, CD4+ cell counts, genotypic resistance tests results, and antiretroviral therapy in a patient with primary HIV-1 resistance. (
  • Management of Persons With Primary Genotypic Resistance. (
  • [5] Fourth, genotypic resistance testing prior to choosing initial therapy is likely to be cost-effective. (
  • Clinical significance of baseline genotypic resistance in FTC-301A. (
  • Genotypic resistance testing was done only after the study was completed. (
  • Measurement of HIV virus load and genotypic resistance by gene amplification in asymptomatic subjects treated with combination therapy. (
  • Genotypic resistance testing is preferred for this purpose (AIII) . (
  • Results Applying our 'DBS-NGS-genotypic resistance test', baseline HIV-1 drug resistance data were successfully obtained from 82.8% (298/360) of newly diagnosed individuals. (
  • These observations have an impact on discussions of the relevance of HIV resistance testing to clinical practice. (
  • However, testing of HIV resistance is not straightforward because the best analysis strategies have not been defined and remain the topic of intense clinical investigation. (
  • 2000). In 1999, the Adolfo Lutz Institute (IAL), with the support from the São Paulo State STD/AIDS Program, has initiated the monitoring of HIV resistance and, in 2000, the use of genotype testing with salvage therapy recommendation to support clinical decision in patients with advanced disease has been established in a limited scale. (
  • Available clinical end-point data clearly indicate that combination therapy is superior to monotherapy, with clinical and surrogate marker data supporting the use of triple drug (or double protease inhibitor) combinations over double nucleoside analogue combinations. (
  • Recent advances in the field of viral entry have led to the development of antiviral agents that target several discrete steps in the viral entry process, a number of which are in clinical trials ( 37 ). (
  • Olson MT, Breaud A, Harlan R, Emezienna N, Schools S, Yergey AL, Clarke W. Alternative calibration strategies for the clinical laboratory: application to Nortriptyline therapeutic drug monitoring. (
  • Additional CD4 cell count and plasma viral load monitoring should be performed for evaluation of children with suspected clinical, immunologic, or virologic deterioration or to confirm an abnormal value (AIII) . (
  • Our data suggest that routine drug-resistance testing of patients who present to a health care provider stating that they are antiretroviral naive prior to initial antiretroviral therapy would be a cost-effective clinical practice. (
  • These high rates were most likely the result of both transmitted resistance and informal antiretroviral use, and they suggest that routine resistance testing among antiretroviral-naive patients would be a cost-effective clinical practice. (
  • To address the question of whether drug-resistance testing should be routinely implemented in clinical practice, San Diego County funded a pilot program to offer standard genotypic drug-resistance testing for all antiretroviral-naive individuals who received HIV-related medical care through San Diego County public funding from 1 January 2005 to 31 December 2005. (
  • The genotyping assays that are currently Food and Drug Administration (FDA)-approved, ViroSeq HIV-1 Genotyping System v. 2.0 (Celera Diagnostics, Alameda, CA) and TRUGENE HIV-1 Genotyping Kit (Bayer HealthCare LLC, Berkeley, CA), provide positive and negative run controls that are to be amplified and sequenced with each batch of clinical samples. (
  • There are a few clinical trials that show a possible decrease in the duration of the active disease state, as well as a decrease in viral shedding and complications. (
  • In a clinical trial, an HIV-positive patient was conditioned by non-lethal doses of irradiation and a chemotherapeutic drug prior to receiving donor. (
  • Antiretroviral treatment may lead to the emergence of HIV drug resistance, which can be transmitted. (
  • However, viral eradication is not achievable with current strategies ( 3 ), and the shift in treatment paradigm to one of long-term viral suppression has led to the challenge of ensuring continuous treatment benefit and avoiding failure ( 4 ). (
  • However, treatment failure is not only viral resistance. (
  • Although treatment failure is a complex phenomenon, viral resistance indeed remains a major issue. (
  • Generally considered less harmful to normal cells than chemotherapy and radiation, these promising drugs can produce rapid and dramatic reductions in the disease burden of certain metastatic cancers, but in most cases tumors rebound several months after treatment due to acquired drug resistance. (
  • Furthermore, the findings might help quantify the overall genetic heterogeneity of resistance prior to treatment and thus may be applied to designing treatment strategies aimed at controlling resistance, according to the authors. (
  • Treatment should be considered as early as practical, and may be best guided by measurement of viral load, with a range of other markers having potential utility in individualising treatment decisions. (
  • Research on new therapies must also assess the metabolic complications and long-term effects of antiretroviral treatment. (
  • Drug resistance patterns following pharmacy stock shortage in Nigerian Antiretroviral Treatment Program. (
  • Development of drug resistance in HIV infected children with Treatment failure is a major impediment to selection of appropriate therapy. (
  • This series examines optimization of antiretroviral therapy in a treatment-experienced patient with HIV, or in a treatment-naive patient with a particularly challenging initial presentation. (
  • Recently, antiretroviral treatment as prevention is an exciting area of progress in HIV-1 research. (
  • Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. (
  • HIV treatment is life-long and lowering the number of drugs people must take could potentially reduce pill burden, side-effects and cost. (
  • For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied. (
  • In a separate analysis that considered treatment-related drug discontinuation as failure, but not discontinuation for other reasons, response rates were higher, at 96.6% and 96.4%, respectively. (
  • There were 11 cases of confirmed virologic withdrawal in the dual therapy group and seven in the triple therapy group, none of whom developed treatment-emergent resistance. (
  • Tyzeka is indicated for the treatment of chronic hepatitis B in adult patients with evidence of viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. (
  • Various immunotherapeutic strategies including structured treatment interruptions, therapeutic immunization, and immunomodulatory agents have been explored with limited success to date [ 11 ], and serve to highlight the complexity of the interaction between host immunity, virus replication and drug efficacy. (
  • Antiretroviral (ARV) drug-resistance testing is recommended at the time of HIV diagnosis, before initiation of therapy, in all treatment-naive patients (AII) . (
  • Viral co-receptor (tropism) assays are recommended whenever a CCR5 antagonist is being considered for treatment (AI*) . (
  • Other areas of interest included host factors that influence virus replication, in-depth analysis of virus transcription and its effect on host gene expression, and multiple discussions of virus pathology, epidemiology as well as new avenues of diagnosis and treatment. (
  • A dynamic stress model explains the delayed drug effect in artemisinin treatment of Plasmodium falciparum. (
  • Therefore, novel anti-HIV agents exhibiting distinct resistance patterns, and favorable pharmacokinetic as well as safety profiles are needed to provide more treatment options. (
  • Until the recent approval of adefovir dipivoxil, lamivudine (a dideoxycytidine analog in the unnatural l configuration) was the only approved oral therapy for the treatment of chronic hepatitis B. Antiviral therapy for chronic hepatitis B with famciclovir and lamivudine has been limited by the emergence of viral resistance in significant proportions of patients. (
  • The adult studies were conducted in clinically advanced, 3-class antiretroviral (NRTI, NNRTI, PI) treatment-experienced adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy . (
  • Treatment interruption strategies should be considered highly experimental and risky due to the potential for developing drug resistance in some cellular or organ compartments, reseeding immune system reservoirs with newly rebounded HIV, acute HIV symptoms, and a decrease in the CD4 count that can lead to life-threatening AIDS opportunistic conditions. (
  • Another is SIT or Structured Intermittent Therapy, which refers to stopping and starting treatment at regular time intervals, without regard to viral loads or CD4 counts. (
  • In October 2007, the United States Food and Drug Administration (FDA) approved the first drug in the integrase-inhibitor class for the treatment of HIV-1 as part of combination antiretroviral therapy in treatment-experienced patients, adding to the available chemotherapeutic agents for the effective treatment of HIV/AIDS. (
  • Analysis of different variables showed that the patients who transitioned in previous years were in more advanced stages of the disease, while those who are currently in the program had received a lower number of rotations of antiretroviral treatment schemes and more often had normal CD4+ lymphocyte counts >500/mm3 (72,1% vs 61,6%, p=0,03). (
  • For example, an early AI application proposed for drug treatment strategy selection was the computer-based consultation system, MYCIN [3]. (
  • HIV viral suppression and geospatial patterns of HIV antiretroviral therapy treatment facility use in Rakai, Uganda. (
  • Although a number of anti HIV drugs have been approved, there are still problems with toxicity and drug resistance. (
  • Such a planned approach, based on consideration of the likely modes of therapeutic failure (viral resistance, cellular resistance, toxicity) could be called rational sequencing. (
  • In vitro phenotypic susceptibilities to indinavir were determined for 38 viral isolates from 13 patients who experienced virologic rebounds during indinavir monotherapy. (
  • After virologic failure, all Envs acquired resistance to ENF but exhibited no consistent change in their sensitivity to the fusion inhibitor T-1249 or to coreceptor inhibitors. (
  • The results were that, after one STI, 46% of the patients spontaneously 'controlled' HIV with an undetectable viral load for a minimum duration of over 2 months, up to a maximum of approximately 15 months. (
  • Since it is greatly difficult to eradicate HIV-1 after the establishment of viral latency, it is necessary to investigate strategies that may close the door to HIV-1. (
  • On Wednesday, May 30, 2018 the HHS Antiretroviral Guideline Panels issued these recommendations regarding the use of dolutegravir in adults and adolescents with HIV who are pregnant or of child-bearing potentia l. (
  • Artificial intelligence in drug combination therapy Tsigelny, Igor F 2018-02-09 00:00:00 Abstract Currently, the development of medicines for complex diseases requires the development of combination drug therapies. (
  • Multiple infections were mostly composed by a mixture of recombinant viruses (94%), with only one case in which protease gene pure subtypes B and F were recovered. (
  • Insufficient drug potency, non-compliance, restricted tissue penetration and drug-specific limitations within certain cell types (e.g. most nucleoside analogs cannot be phosphorylated in resting cells) may account for the incomplete suppression of sensitive viruses. (
  • Phenotypic assays measure the IC50 of the drug against the virus in vitro. (
  • The T20 expression vector may be used in a variety of therapeutic applications, such as ex vivo transfection of dendritic cells to induce a host immune response to HIV, localized transfection in vivo in a gene therapy approach to provide longer term delivery of T20, or in vitro production of T20 peptide. (
  • In vitro, maraviroc demonstrates no antagonism with existing antiretroviral agents and additive or synergistic activity in combination with enfuvirtide. (
  • This year, the US Department of Health and Human Services (DHHS) recommended that drug resistance testing be performed prior to the initiation of antiretroviral (ARV) therapy, ideally at the time of initial diagnosis. (
  • Drug-resistance testing before initiation of antiretroviral therapy in antiretroviral-naive patients is cost-effective when the prevalence rate of transmitted drug resistance is 8%-10% [7]. (
  • This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. (
  • This results in the formation of immature, noninfectious viral particles. (
  • Current knowledge and future discoveries will make it necessary to study a huge number of genes that could be involved in a genetic predisposition to cancer. (
  • Partial pol and env genes were sequenced and used for phylogenetic, genetic tropism, and genotypic drug resistance analyses. (
  • An example is the genetic disease, sickle cell anaemia, characterized by pain leading to organ damage due to defect in haemoglobin of the red blood cell, which occurs as a result of change of a single base, thymine, to adenine in a gene responsible for encoding one of the protein chains of haemoglobin. (
  • Although all cells in an organism have the same genetic material different genes are expressed. (
  • For the drugs, hundreds of 2D and 3D molecular descriptors for medicines are now available, while for patients, large data sets related to genetic/proteomic and metabolomics profiles of the patients are now available, as well as the more traditional data relating to the histology, history of treatments, pretreatment state of the organism, etc. (
  • Varying degrees of HIV-1 cross-resistance have been observed between indinavir and other HIV-1 protease inhibitors. (
  • But antiretroviral therapy that uses just two drugs requires agents that are strong enough keep viral load fully suppressed and prevent the development of drug resistance. (
  • HIV replicating within the brain causes neurocognitive disorders in up to 20-30% of infected individuals and is a viral sanctuary site for the development of drug resistance. (
  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals [see WARNINGS AND PRECAUTIONS ]. (
  • Antiretroviral therapy, with nucleoside analogues (acyclovir, valacyclovir, and famciclovir), act as competitive inhibitors and chain terminators of DNA synthesis. (
  • Resistance to either NRTI or NNRTI among the recently is a new challenge that needs to be addressed. (
  • HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. (
  • Binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV. (
  • But scientists are interested in developing therapies that aim for host proteins instead, or the genes that produce them, in part because such therapies are believed less likely to elicit drug resistance. (
  • Their approach entails disrupting host genes rather than proteins. (
  • It is based on the idea, pioneered by Krogan, that you obtain richer information about the functions of genes--and the proteins they encode--when you disable the genes in pairs, instead of one by one. (
  • In particular, they used the genes encoding a large number of human proteins that the Krogan lab had previously found to bind to HIV proteins. (
  • HIV-1 also has regulatory genes ( tat and rev ) and genes that encode for accessory proteins ( vpu , vpr , vif , and nef ) that are important in viral replication and interaction with the host. (
  • Genes, proteins or chemicals that can act as signals for certain diseases. (
  • Low prevalence of transmitted HIV-1 drug resistance detected by a dried blood spot (DBS)-based. (
  • Conclusions The prevalence of transmitted HIV-1 drug resistance is currently low in the study sites in Cameroon. (
  • most public health agencies in the United States do not routinely offer drug-resistance testing to antiretroviral-naive patients, although the prevalence of primary drug resistance has been documented at rates higher than this threshold [2, 3]. (
  • Research cohort studies of individuals who were recently infected with HIV in the United States, Canada, Mexico, and Europe have reported prevalence of transmitted drug resistance of 8.3%-20% [1-6]. (
  • This screening assay takes 4 days to complete and multiple compounds can be screened in parallel. (
  • A recombinant virus assay initially developed to measure antiretroviral drug resistance during a single round of virus replication was adapted to measure virus-antibody neutralization ( 19 ). (
  • Use of sequencing-based genotyping as a diagnostic assay for human immunodeficiency virus (HIV) antiretroviral resistance is increasing. (
  • As ART programs in sub-Saharan Africa continue to expand, individuals on ART should be closely monitored for the emergence of drug resistance. (
  • However, M184V outcompetes M184I within several weeks of viral replication and is found in most patients with virological failure on 3TC or FTC ( 39 , 31 ). (
  • Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. (
  • Using a large sample of schizophrenia patients and controls and a battery of tasks across multiple cognitive domains, we examined whether patients show accelerated age-related decline in cognition and whether an age-related effect differ between females and males. (
  • Distinct pattern of TAMs with K65R in patients failing tenofovir-based antiretroviral therapy. (
  • The purpose of this study determine whether the drug valganciclovir has a significant and real benefit on the central core of symptoms experienced by patients who have high titers to EBV and HHV-6 and are experiencing long-standing fatigue and cognitive impairment (CFS). (
  • The concept that drug efficacy can be augmented by strong antiviral immune responses is compelling, and has led to efforts to stimulate antiviral immunity in HIV-infected patients on ART. (
  • The effect of high-dose saquinavir on viral load and CD4+ T-cell counts in HIV-infected patients. (
  • However, despite these impressive results, 30 to 50% of patients ultimately fail combination drug therapies. (
  • This meant that the other half of patients did not control HIV during the first STI and had viral rebound that did not spontaneously decrease. (
  • Since then, significant understanding of HIV pathogenesis has occurred and the development of drug treatments now significantly extend patients' lives. (
  • More recently, over the past several years, there has been an explosion in the available information related to the properties of drugs and the biomedical parameters of patients. (
  • But investment and development of new antibiotics have not kept pace with current and potential antibiotic resistance around the world. (
  • Current areas of particular interest are in HIV, and in antibiotic resistance. (
  • The evolution of antibiotic resistance in a structured host population. (
  • Here, we develop a new model of the evolution of antibiotic resistance in a commensal bacterial population adapting to a heterogeneous host population composed of untreated and treated hosts, and structured in different host classes with different antibiotic use. (
  • Session 4 dealt with anti-viral drugs and vaccination and session 5 evoked epidemiological aspects of HIV and HCV transmission. (
  • Moreover, by carrying out these pairwise disruptions across hundreds of genes, scientists can find groups of genes with similar patterns of interactions, a sign that they are likely to take part in the same molecular process. (
  • Various bioinformatics methods attempt to cluster these expression patterns in order to find groups of genes that have similar expression over numerous samples. (
  • However, analyses of mycobacterial interspersed repetitive unit-variable-number tandem-repeat typing, along with insertion sequence 6110 restriction fragment length polymorphism analyses of the pretreatment drug-susceptible strain and the week 12 MDR strain, showed distinct spoligotypes. (
  • We were able to identify and quantify the molecular footprint of drug-selective pressure in pol using maximum likelihood inference under different codon substitution models. (
  • The durability of response to protease inhibitor therapy is predicted by viral load [abstract no. 62]. (
  • Samples with multiple infections were cloned, and sequence data submitted to phylogenetic analysis. (
  • We were able to identify 17 HIV-1 multiple infections out of 47 samples. (
  • Most current drugs against viral infections target the virus itself. (
  • These viral infections all have important human, social and political consequences worldwide. (
  • In particular, insulin resistance and liver damage in the pathophysiology of HCV and HIV infections are prominent. (
  • Acute viral hepatitis follows three distinct phases: The initial prodromal phase (preceding symptoms) involves non-specific and flu-like symptoms common to many acute viral infections. (
  • The development of a fixed dose combination aims to reduce the number of daily tablets, and therefore enhance adherence to therapy and thereby minimizing the risk of emergence of resistance. (
  • HA060 trade name] is a generic version of Combivir®, the first fixed-dose combination containing two known antiretroviral agents belonging to the RT inhibitors class. (
  • The combination of these morphologic changes and antiretroviral-associated metabolic derangements has been referred to as the lipodystrophy syndrome ( Figures 1-4 ). (
  • The database interface utilizes a faceted interface, allowing real-time combination of multiple search parameters to assemble a meta-dataset, which can be downloaded for further analysis. (
  • It demonstrates additive or synergistic activity in combination with other approved antiretroviral agents. (
  • Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations. (
  • In this review, we discuss several AI methods that have been successfully implemented in several instances of combination drug therapy from HIV, hypertension, infectious diseases to cancer. (
  • ViiV Healthcare's dolutegravir is a potent integrase inhibitor with a high barrier to resistance. (
  • 13,14 When integrase is inhibited, host enzymes circularize the viral cDNA, and 2-long terminal repeat (LTR) circles accumulate in the nucleus. (
  • Assuming that the viral phylogeny should be consistent with the "true" transmission history, transmission chains allow assessment of the accuracy and reliability of phylogenetic reconstructions ( 19 ). (
  • The pediatric population in particular is not only at a higher risk of developing resistance (due to greater viral loads and difficulty in adherence and accurate dosing), but resistance proves a greater challenge as they require longer term therapy than adults. (
  • Ritonavir's function is not primarily to further contain HIV but rather to increase the blood levels of the second PI, decrease pill burden, simplify dosing schedules, and thereby improve drug adherence . (
  • The fact that both Y181C isolates are IDUs is important and represents 2/21 (~10%) NNRTI drug resistance. (
  • However, the use of these new drugs is complicated by the fact that they target, either directly or indirectly, the highly variable viral envelope (Env) protein. (
  • The introduction of highly active antiretroviral therapy in industrialized nations has brought about dramatic declines in the incidence of AIDS-associated complications, including PCP. (
  • He has served on multiple VA and NIH/NCI review panels and is a current member of the DHHS/NIH Panel on Antiretroviral Guidelines for Adults and Adolescents. (
  • The majority of antibodies directed against the viral envelope glycoprotein (Env) recognizes nonneutralizing epitopes of glycoprotein monomers and is ineffectual ( 2 , 3 ). (