• Our model also allows quantification of the selective advantage of mutations by integrating their effects on viral fitness and drug susceptibility. (plos.org)
  • A viral quasispecies is a population structure of viruses with a large number of variant genomes (related by mutations). (wikipedia.org)
  • The finding that a viral population was essentially a pool of mutants came at a time when mutations in general genetics were considered rare events, and virologists associated a viral genome with a defined nucleotide sequence, as still implied today in the contents of data banks. (wikipedia.org)
  • In a recent study in public and private detect mutations associated with resistance. (cdc.gov)
  • Combination therapy has been shown to dramatically reduce the likelihood of drug resistance (many drug-resistant mutations are mutually exclusive) and to suppress viral replication to the point that progression to AIDS is significantly slowed. (medscape.com)
  • Antiviral-resistance mutations often affect more than one drug simultaneously because of similar development pipelines and the ultimate molecular structure of the drug, and combination choices should account for this possibility. (medscape.com)
  • What we've tried to do is consider in the strategy as many resistance mutations as we're aware of. (acs.org)
  • Dolutegravir-based treatment in PLHIV with pre-existing nucleoside reverse transcriptase inhibitor-mutations was non-inferior to protease inhibitor-based regimens. (lu.se)
  • In a systematic review of 30 studies from low-income settings in 2011 [ 5 ], 80% and 88% of children failing first-line ART had 1 or more International AIDS Society (IAS)-USA major nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations, respectively. (prolekare.cz)
  • No integrase strand inhibitor (INSTI) resistance-associated mutations were reported. (jnj.com)
  • The main objective was to study drug resistance mutations (DRM) in the HIV-1 reverse transcriptase (RT) gene of minor HIV-1 quasispecies, not detectable with standard techniques. (avhandlingar.se)
  • However, little data is available on the evolution, interaction and linkage of drug resistance mutations throughout the pol gene. (ucl.ac.uk)
  • In this study, we developed a single genome sequencing assay of the full-length HIV-1 pol gene and used it to investigate the development and linkage of drug resistance mutations in sequential samples from two patients failing INSTI-containing salvage therapy. (ucl.ac.uk)
  • Different phylogenetic methods were used to explore the evolution and dynamics of drug resistance mutations in the full-length HIV-1 pol gene. (ucl.ac.uk)
  • Our data indicate that the development of drug resistance mutations in IN is complex and is a fine balance between attaining high levels of drug resistance and decent replicative fitness. (ucl.ac.uk)
  • Identification of baseline resistance mutations allows for the selection of more effective and durable antiretroviral (ARV) regimens. (hiv.gov)
  • Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. (unl.pt)
  • We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program. (unl.pt)
  • Resistance of NNRTIs occurs through mutations of the reverse transcriptase gene in the viral genome. (antimicrobe.org)
  • HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. (ox.ac.uk)
  • Drug resistance largely results from changes (mutations) in the genetic material that code for these enzymes, rendering ART less effective. (canada.ca)
  • Most mutations do not result in the development of drug resistance, as they are lethal, reduce fitness, or even if not affecting viral growth, occur at sites that are not targeted by ART. (canada.ca)
  • However, under conditions in which treatment does not completely inhibit viral replication, a virus with drug-resistant mutations may begin to thrive, resulting in treatment failure. (canada.ca)
  • Genotypic tests identify mutations in the viral genetic material through sequencing the viral genes of interest. (canada.ca)
  • By comparing the generated sequences with databases containing resistance-conferring mutations, the presence or absence of drug resistance can be determined. (canada.ca)
  • The percentage of individuals with protocol-defined confirmed virologic withdrawal (CVW) was 1.7% (12/716) in the dolutegravir plus lamivudine arm and 1.3% (9/717) in the dolutegravir plus TDF/FTC arm.1 None of these participants developed treatment-emergent resistance mutations. (natap.org)
  • Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis. (scienceopen.com)
  • To investigate the extent to which drug resistance mutations are missed by standard genotyping methods, we analyzed the same plasma samples from 26 patients with suspected multidrug-resistant human immunodeficiency virus type 1 by using a newly developed single-genome sequencing technique and compared it to standard genotype analysis. (scienceopen.com)
  • A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. (aidsmap.com)
  • The first clinical description of HIV resistance to an antiretroviral agent was published in 1989, when patients taking zidovudine monotherapy accumulated mutations within the reverse transcriptase gene, resulting in a marked increase in drug resistance [ 1 ]. (medilib.ir)
  • The interpretation of these tests and the approach to selecting an antiretroviral therapy regimen for patients with drug resistance mutations are discussed elsewhere. (medilib.ir)
  • Genotypic resistance assays detect the presence of specific drug resistance mutations in the regions of the HIV genome encoding protease, reverse transcriptase, and integrase. (medilib.ir)
  • Results are reported as the individual mutations (eg, M184V, the signature mutation for lamivudine resistance) with comments such as "susceptible," "possibly resistant," or "resistant" for each antiretroviral agent. (medilib.ir)
  • The susceptibility that is measured with phenotypic assays is the aggregate of the acquired drug mutations in a patient's viral strain [ 6 ]. (medilib.ir)
  • Genotypic assays provide information on the specific resistance mutations present within the virus. (medilib.ir)
  • However, in treatment-experienced patients with multiple resistance mutations, interpreting complex genotypes can be challenging since it can be difficult to interpret the clinical significance of a specific mutation when many mutations are present. (medilib.ir)
  • As an example, some mutations cause resistance to certain drugs but increase susceptibility to others, while other mutations may impact viral fitness (see "Interpretation of HIV drug resistance testing", section on 'Viral fitness' ). (medilib.ir)
  • For such patients, phenotypic resistance testing may have an advantage over genotypic testing, as it measures resistance more directly and can assess relative susceptibility and interactions among mutations. (medilib.ir)
  • Baseline genotype testing reveals no HIV drug-resistant mutations. (medscape.com)
  • Quasispecies result from high mutation rates as mutants arise continually and change in relative frequency as viral replication and selection proceeds. (wikipedia.org)
  • Islatravir is a nucleoside transcription translocation inhibitor, it has a long half life, inhibits viral replication, and its multiple mechanisms of action contribute to its high potency and high barrier to resistance, including drug resistant viruses. (theseoultimes.com)
  • Although antiretroviral therapy (ART) can effectively inhibit replication of human immunodeficiency virus type 1 (HIV-1), the virus is able to persist in cellular and anatomical viral reservoirs. (avhandlingar.se)
  • The involvement of viral DNA-binding proteins in the regulation of virulence genes, transcription, DNA replication, and repair make them significant targets. (mdpi.com)
  • HIV is grouped into the genus Lentivirus (lentus, from Latin) due to the slow course of infection and thus disease, with a long latency period, persistent viral replication and central nervous system involvement ( 1 ). (scielo.sa.cr)
  • Phenotypic resistance assays measure the extent to which an antiretroviral drug inhibits virus replication in vitro. (medilib.ir)
  • Similar to bacteriologic methods, this is typically performed by demonstrating an increase in the inhibitory concentration (IC) that is required to inhibit in vitro growth by 50 percent (IC50) compared with virus replication in the absence of drug. (medilib.ir)
  • His work has shown that a viral exonuclease has a chief role in proofreading nucleotide mismatches that occur during viral RNA replication and that this proofreading provides coronaviruses with natural resistance to many nucleoside analogue drugs. (wisc.edu)
  • These drugs work by blocking the activity of a specific enzyme called protease, which is essential for the replication of HIV. (meds4uonline.su)
  • These drugs work together to target different stages of the viral replication process, providing a more comprehensive approach to controlling the infection. (meds4uonline.su)
  • One other important viral factor is the genetic barrier to resistance related to the number and type of nucleotide substitutions required for the emergence of RASs during replication. (biomedcentral.com)
  • A lot of us were pushing for this approach back in the late 1990s because the biology was coming out saying that it was viral replication, this ongoing onslaught to the immune system of 1 to 10 billion viruses produced a day. (medscape.com)
  • Antiretroviral therapy does not cure HIV infection but suppresses viral replication within a person's body and allows an individual's immune system to strengthen and regain the capacity to fight off infections. (who.int)
  • The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set an ambitious target for 2020: that 90% of people living with HIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), and 90% receiving ART have viral load (VL) suppression [ 1 ]. (prolekare.cz)
  • The only large randomised trial to date of second-line ART in African adults found that those receiving NRTI-based second-line regimens had equivalent virological suppression to those receiving regimens based on 2 new drug classes [ 7 ], suggesting that NRTI cross-resistance may have less relevance than feared. (prolekare.cz)
  • The first was to directly compare children randomised to monitoring with and without CD4 counts in terms of long-term VL suppression and resistance. (prolekare.cz)
  • This 2-drug long-acting injectable antiretroviral-based regimen for maintenance of viral load suppression consists of Rilpivirine (a non-nucleoside reverse transcriptase inhibitor) and Cabotegravir (an integrase inhibitor). (theseoultimes.com)
  • Once the decision to initiate antiretroviral therapy has been made, treatment should be aggressive with the goal of maximal viral suppression. (cdc.gov)
  • For those who chose anti-retroviral treatment, especially those who took early monotherapy and duotherapy options that facilitated the development of resistant virus, survival was sometimes about hanging on until a newer, more powerful class of drugs was released and hoping they would result in viral suppression and increased T cells with few side effects if our current combo was no longer effective. (poz.com)
  • The filing is based on the results from the phase III TANGO study, which demonstrated adults living with HIV-1, who had maintained virologic suppression for at least six months on a tenofovir alafenamide fumarate (TAF)-containing regimen of at least three drugs, were able to maintain similar rates of virologic suppression after switching to the two-drug regimen (2DR) Dovato, compared to those who continued the TAF-containing regimen. (viivhealthcare.com)
  • Dolutegravir plus lamivudine continues to demonstrate long-term non-inferior efficacy compared to dolutegravir plus TDF/FTC with benefits beyond viral suppression. (natap.org)
  • The momentum behind 2DRs is growing: Dovato has now shown sustained efficacy and tolerability through three years of treatment, with people able to maintain viral suppression with fewer medicines than a 3-drug regimen. (natap.org)
  • Switching to Reyataz from other protease inhibitors maintains viral suppression and results in fewer viral rebounds, improved gastrointestinal tolerance, and significant lipid improvements, according to a study presented at the Third International AIDS Society Conference on HIV Pathogenesis and Treatment. (hivplusmag.com)
  • Objective: The purpose of this survey was to estimate the prevalence of viral load (VL) suppression and emergence of HIV drug resistance (HIVDR) among individuals receiving antiretroviral therapy (ART) for 36 months or longer in Viet Nam using a nationally representative sampling method. (who.int)
  • RATIONALE FOR HIV SUSCEPTIBILITY TESTING - The use of HIV susceptibility testing to guide therapy leads to better viral suppression and has been associated with improved survival [ 2-5 ]. (medilib.ir)
  • The 3rd 90′ of UNAIDS 90:90:90 targets 90% viral suppression for persons on ART. (biomedcentral.com)
  • In order to promptly switch treatment and to ensure sustained virologic suppression, viral load (VL) monitoring to identify virologic failure is crucial. (biomedcentral.com)
  • Through mathematical modeling, we assess the mechanisms by which HIV-1 can develop resistance against nucleoside analog reverse transcriptase inhibitors (NRTI). (plos.org)
  • We correctly predict that HIV-1 can develop resistance by decreasing NRTI incorporation rate, increasing its excision rate, or decreasing its affinity for the viral polymerase enzyme. (plos.org)
  • In 2012, WHO reported that 60% and 67% of adults and children in sub-Saharan Africa failing first-line ART at 12 months had NRTI and NNRTI resistance, respectively [ 6 ]. (prolekare.cz)
  • If approved, this treatment could be the first two-drug regimen for HIV and could offer those living with HIV who are virally suppressed the option to switch to a regimen which does not include a nucleotide reverse transcriptase inhibitor (NRTI). (jnj.com)
  • the nucleoside analogue RT inhibitor (NRTI) lamivudine (3TC) and the non-nucleoside RT inhibitors (NNRTIs) efavirenz (EFV) and nevirapine (NVP). (avhandlingar.se)
  • If the NRTI abacavir (ABC) is considered as part of treatment, HLA-B*5701 must be obtained and ABC only prescribed if the patient is negative for this haplotype, as persons who are positive are at risk for a potentially serious hypersensitivity reaction to the drug. (medscape.com)
  • 50c/mL for at least six months, without prior virologic failure, no historical nucleoside reverse transcriptase inhibitors (NRTI) or integrase inhibitor (INI) major resistance mutation, and no evidence of hepatitis B infection. (viivhealthcare.com)
  • Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI), and tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor (NtRTI). (aidsmap.com)
  • We therefore investigated virological outcomes and resistance in the ARROW randomised trial (ISRCTN24791884), which compared first-line ART regimens and CD4 monitoring strategies in children and adolescents in Uganda and Zimbabwe [ 8 ]. (prolekare.cz)
  • The SWORD Phase III results represent an important step forward in our efforts to deliver a two-drug regimen that may help simplify dosing regimens and reduce pill burden for people living with HIV," says Lawrence M. Blatt, Global R&D Head, Infectious Diseases & Vaccines, Janssen. (jnj.com)
  • Drug resistant HIV may severely restrict therapeutic options, and treatment costs will greatly increase when more people need second and third line antiretroviral regimens. (bmj.com)
  • OBJECTIVE: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy regimens in programs without routine viral load (VL) monitoring and to examine intersubtype differences in DRMs. (ox.ac.uk)
  • In particular, higher rates of etravirine and rilpivirine resistance in subtype-C may limit their potential utility in salvage regimens. (ox.ac.uk)
  • These long-term data confirm that dolutegravir-based 2-drug regimens have a rightful place in the HIV treatment compendium. (natap.org)
  • A four-nucleoside regimen containing Viread and Trizivir following treatment failure with protease inhibitor- or nonnuke-based regimens is effective in reducing blood-based viral counts to below 400 copies in 87% of adults and to below 50 copies in 59% of adults, according to a study presented at the Third International AIDS Society Conference on HIV Pathogenesis and Treatment. (hivplusmag.com)
  • The mean time on ART was 75.5 months (95% confidence interval [CI]: 69.0-81.9 months), and 93.7% of the patients were receiving non-nucleoside reverse transcriptase inhibitor-based regimens. (who.int)
  • The evolution of drug resistance has significant clinical implications for choosing effective antiretroviral regimens. (medilib.ir)
  • Nucleoside analogs ( NA s) are used to treat numerous viral infections and cancer. (plos.org)
  • Nucleoside analogs ( NA s) represent an important drug class for the treatment of viral infections and cancer. (plos.org)
  • von Kleist M, Metzner P, Marquet R, Schütte C (2012) HIV-1 Polymerase Inhibition by Nucleoside Analogs: Cellular- and Kinetic Parameters of Efficacy, Susceptibility and Resistance Selection. (plos.org)
  • The mechanism of HBV resistance to nucleoside analogs are described as well as the concept for multiple drug therapy and combination with immunostimulatory approaches. (nih.gov)
  • The overuse of nucleoside analogs, such as acyclovir (ACV), which suppresses viral DNA polymerase, has led to drug resistance. (molvis.org)
  • This is primarily due to poorly characterized RNA polymerases and weak clinical activity of nucleoside analogs (ribavirin for respiratory syncytial virus [RSV] and parainfluenza). (ccjm.org)
  • In general, a protease inhibitor and two non-nucleoside reverse transcriptase inhibitors should be used initially. (cdc.gov)
  • Therapy should involve combinations of drugs-two nucleoside-analogue reverse-transcriptase inhibitors combined with either a protease inhibitor (PI) or a non-nucleoside-analogue reverse-transcriptase inhibitor. (medscape.com)
  • CONCLUSIONS: Non-B subtypes differ in DRMs at first-line failure, which impacts on residual nucleoside reverse transcriptase inhibitor and NNRTI susceptibility. (ox.ac.uk)
  • The FDA has given fast-track approval designation to the experimental protease inhibitor GSK-640385, being developed by GlaxoSmithKline, based on data from a Phase IIa clinical trial showing the drug was effective against strains of HIV resistant to other protease inhibitors. (hivplusmag.com)
  • A six-month Phase II clinical trial of the Incyte experimental nucleoside reverse transcriptase inhibitor Reverset showed the drug reduced HIV viral loads by more than 90% in more than half of all study subjects who had built up resistance to other anti-HIV medications. (hivplusmag.com)
  • ViiV Healthcare, the global specialist HIV company, majority owned by GlaxoSmithKline, with Pfizer Inc. and Shionogi Limited as shareholders, today announced that the European Commission has granted Marketing Authorisation for Dovato (dolutegravir/lamivudine) for the treatment of HIV-1 infection in adults and adolescents above 12 years of age weighing at least 40 kg, with no known or suspected resistance to the integrase inhibitor class, or lamivudine. (gsk.com)
  • Dovato (dolutegravir 50 mg/ lamivudine 300 mg tablets) is authorised in the EU for the treatment of HIV-1 infection in adults and adolescents above 12 years of age weighing at least 40 kg, with no known or suspected resistance to the integrase inhibitor class, or lamivudine. (gsk.com)
  • In case of adults, this includes patients on a first-line, non-nucleoside reverse transcriptase (NNRTI)-based regimen, or on a second-line, protease inhibitor (PI)-based regimen, and in case of children, this includes patients on a first-line PI-based regimen. (sun.ac.za)
  • In particular, 421 V associated with resistance to non-nucleoside inhibitor beclabuvir was polymorphic in Europe and USA, being detected in 24% and 11% of sequences, respectively, P = 0.0140. (biomedcentral.com)
  • 50 c/mL) on a stable antiretroviral regimen for at least six months with no history of virological failure and no known or suspected resistance to any non-nucleoside reverse transcriptase inhibitor (NNRTI) or integrase strand transfer inhibitor (INSTI). (jnj.com)
  • Insulin resistance (IR) is common in HIV-seropositive patients, particularly among those receiving protease inhibitor (PI) and is more prevalent among those with lipoatrophy or fat accumulation in the visceral region. (bvsalud.org)
  • The common AIDS drugs AZT (zidovudine) and 3TC (lamivudine) belong to this class of pharmaceuticals. (acs.org)
  • Research Triangle Park, US, 16 October 2019 - ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, announced the submission of a supplemental New Drug Application to the US Food and Drug Administration (FDA) for Dovato (dolutegravir and lamivudine) as a switch treatment for HIV-1 infection in virologically suppressed adults on a stable antiretroviral regimen with no treatment failure. (viivhealthcare.com)
  • In the US, Dovato is currently approved as a complete, once-daily, single-tablet regimen of dolutegravir (DTG) 50 mg and lamivudine (3TC) 300 mg for the treatment of HIV-1 infection in adults with no antiretroviral treatment history and with no known resistance to either DTG or 3TC. (viivhealthcare.com)
  • While overall adverse event rates were similar across the study arms, we saw fewer drug-related adverse events with dolutegravir plus lamivudine. (natap.org)
  • Dolutegravir plus lamivudine continued to demonstrate a high genetic barrier to treatment-emergent resistance. (natap.org)
  • These studies evaluate a 2-drug regimen of dolutegravir plus lamivudine compared with a 3-drug regimen of dolutegravir plus TDF/FTC in HIV-1 infected, antiretroviral treatment-naïve adult participants with baseline HIV-1 viral loads between 1,000 and 500,000 c/mL. (natap.org)
  • Atripla was licensed on the basis of data from Study 934, which compared efavirenz ( Sustiva ), emtricitabine ( Emtriva ) and tenofovir disoproxil fumarate ( Viread ) taken as separate drugs, to the combination of efavirenz and zidovudine (AZT) plus lamivudine (3TC) as Combivir . (aidsmap.com)
  • Four patients (1%) in both the dolutegravir and lamivudine, and the dolutegravir and TDF/FTC, study arms experienced drug-related serious adverse events, and 15 patients (2%) in the dolutegravir and lamivudine arm and 16 patients (2%) in the dolutegravir and TDF/FTC arm had adverse events that led to discontinuation. (gsk.com)
  • This treatment allows individuals to take a two-drug regimen in a single pill with dolutegravir at the core, building on the established potency and safety profiles of dolutegravir and lamivudine. (gsk.com)
  • Dovato (dolutegravir 50 mg/ lamivudine 300 mg tablets) was authorised by the US Food and Drug Administration in April 2019 [5] (please see US Prescribing Information including Box Warning), and further regulatory applications have been submitted worldwide. (gsk.com)
  • In the US the Food and Drug Administration (FDA) authorised Dovato, a complete, once-daily, single-tablet regimen of dolutegravir (DTG) 50 mg and lamivudine (3TC) 300 mg for the treatment of HIV-1 infection in adults with no antiretroviral (ARV) treatment history and with no known resistance to either DTG or 3TC. (gsk.com)
  • These agents are classified according to their chemical structures: the three nucleoside analogues include lamivudine, telbivudine and entecavir, whereas the two nucleotide analogues include adefovir dipivoxil, tenofovir disoproxil fumarate (TDF), [ 2 ] and the newly approved tenofovir alafenamide (TAF). (medscape.com)
  • The NS5b inhibitors are classified into nucleoside/nucleotide inhibitors (Ni) and non-nucleoside inhibitors (NNi). (biomedcentral.com)
  • Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real-life setting. (medscape.com)
  • RT is a viral enzyme that transcribes the virus's single-stranded RNA genome into DNA. (acs.org)
  • Taken together, the data suggests that larger regions of patient-derived HIV-1 genome should be examined in order to get a good understanding of HIV-1 drug susceptibility. (ucl.ac.uk)
  • Structural proteins are all encoded by the 3' terminus of the viral genome. (medsci.org)
  • Therefore, the evolutionary trajectory of the viral infection cannot be predicted solely from the characteristics of the fittest sequence. (wikipedia.org)
  • In an analysis based on the ARROW trial, Alex Szubert and colleagues report on virological and drug resistance outcomes in children with HIV infection. (prolekare.cz)
  • When nonnucleoside reverse transcriptase inhibitors are used as monotherapy for HIV-1 infection, drug resistance develops rapidly. (antimicrobe.org)
  • It is important to obtain testing for drug resistance and hepatitis co-infection before intitiation of ART, as these results can impact choice of regimen. (medscape.com)
  • Higher rates of infection with HIV are exhibited among injection drug users mainly because of unsafe injecting behavior. (benthamscience.com)
  • The Canadian HIV Strain and Drug Resistance Surveillance Program (SDR program) monitors and assesses HIV strains and the transmission of HIV drug resistance among individuals with newly diagnosed and not yet treated HIV infection in Canada. (canada.ca)
  • Primary drug resistance is resistance observed in treatment-naive individuals with newly diagnosed HIV infection, in whom resistance is presumably due to the transmission of a drug-resistant variant of HIV-1. (canada.ca)
  • Accurate identification of the transmitted virus and sequences evolving from it could be instrumental in elucidating the transmission of human immunodeficiency virus type 1 (HIV-1) and in developing vaccines, drugs, or microbicides to prevent infection. (scienceopen.com)
  • These findings indicate that HIV-1 env genes, other viral genes, and even full-length viral genomes responsible for productive clinical infection can be identified by SGA analysis of plasma virus sampled at intervals typical in large-scale vaccine trials and that pathways of viral diversification and immune escape can be determined accurately. (scienceopen.com)
  • Recommendations for Use of Antiretroviral Drugs During Pregnancy , Appendix C: Antiretroviral Counseling Guide for Health Care Providers , and Early (Acute and Recent) HIV Infection in the Adult and Adolescent Antiretroviral Guidelines for more information. (hiv.gov)
  • Conclusions: A combined regimen of short course AZT with intrapartum NVP for PMTCT may, in addition to reducing the risk of neonatal infection, also reduce the risk of NVP resistance in the mothers compared to a regimen of NVP only. (sun.ac.za)
  • These guidelines provide guidance on the diagnosis of HIV infection, the care of people living with HIV and the use of antiretroviral (ARV) drugs for treating and preventing HIV infection. (bvsalud.org)
  • In 2016, WHO released the second edition of the Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. (who.int)
  • Intrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. (biomedcentral.com)
  • This has changed in the last few years with the development and approval for use of second-generation NNRTIs and PIs, and three new classes of drugs including integrase strand transfer inhibitors (INSTIs). (ucl.ac.uk)
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are highly selective for HIV-1 but do not exhibit activity against other viruses. (antimicrobe.org)
  • NNRTIs are suitable for TDM for several reasons, including considerable interpatient variability in concentrations among patients who take the same dose and data indicating relationships between the concentration of drug in the body, the anti-HIV effect and in some cases, toxicity. (antimicrobe.org)
  • NNRTIs), a single mutation may be associated with a high level of resistance to drugs from that same class. (canada.ca)
  • Among the number of NNRTIs approved for use in HIV treatment, EFV is one of the most commonly prescribed drug. (ru.ac.za)
  • This publication provides guidance on the public health response to pretreatment HIV drug resistance (HIVDR) to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) among people without prior antiretroviral (ARV) drug exposure or people with prior ARV exposure who are initiating or reinitiating first. (bvsalud.org)
  • As HIV is increasingly treated as a life-long condition, we remain committed to ongoing research and development of further medicines to treat HIV more simply and to help all those living with HIV to achieve an undetectable viral load and have an improved quality of life. (jnj.com)
  • Once their viral load became undetectable they were given Cabotegravir/ Rilpivirine regimen. (theseoultimes.com)
  • ATLAS study involved people who were already on oral antiretroviral therapy and had undetectable viral load. (theseoultimes.com)
  • Two large observational studies of serodiscordant couples revealed that PLWHA who consistently take ART and maintain undetectable HIV viral loads do not transmit HIV to their sexual partners. (medscape.com)
  • In the European Union and United Kingdom efavirenz/tenofovir (TDF)/emtricitabine is licensed for use in patients who have already achieved undetectable viral load on a combination in which the components are dosed separately as tenofovir (TDF)/emtricitabine and efavirenz. (aidsmap.com)
  • It was also fueled by the fact that a lot of those early drugs, especially in the 1990s and early 2000s, were quite toxic - drugs like zidovudine (AZT) , stavudine (d4T), didanosine (ddI) , and the early protease inhibitors . (medscape.com)
  • HIVdb Program: Genotypic Resistance Interpretation Algorithm [Internet]. (who.int)
  • As an example, in an observational study of more than 2699 HIV-infected patients who were eligible for genotypic and phenotypic testing between 1999 and 2005, resistance testing was associated with improved survival (adjusted hazard ratio, 0.69 [95% CI 0.51-0.94]) after controlling for demographics, CD4 cell count, HIV RNA level, and intensity of clinical follow-up [ 3 ]. (medilib.ir)
  • GENOTYPIC VERSUS PHENOTYPIC ASSAYS - This section will provide an overview of the commonly used resistance assays. (medilib.ir)
  • Overview of the assays - Resistance assays can be categorized as either genotypic or phenotypic. (medilib.ir)
  • See 'Genotypic resistance assays' below. (medilib.ir)
  • Methods: A cross-sectional investigation of genotypic antiretroviral drug resistance in: a) HIV-infected mothers who were exposed to a PMTCT regimen of short course azidothymidine (AZT) with single dose nevirapine (NVP) during labour. (sun.ac.za)
  • In this prospective cohort study of patients who had been on combined antiretroviral therapy treatment (cART) for at least 12 months in Bangui, only one HIV plasma viral load per patient was realized at the Institut Pasteur of Bangui, between April 4th and November 28th, 2017. (scirp.org)
  • The rate of virological failure among patients on cART is very high in the CAR, despite the availability of and access to monitoring of HIV plasma viral load in Bangui. (scirp.org)
  • Plasma viral load is considered as the strongest determinant of sexual transmission of HIV. (benthamscience.com)
  • Booster drugs are used to 'boost' the effects of protease inhibitors and some other antiretrovirals. (aidsmap.com)
  • Protease inhibitors are a class of antiretroviral drugs, which are used to treat HIV infections. (meds4uonline.su)
  • For the developed non-nucleoside drugs (neuraminidase inhibitors and adamantanes for influenza) clinical challenges include short therapeutic windows, limited effects on the severely ill, and drug resistance. (ccjm.org)
  • This resulted in extensive resistance to PIs and reverse transcriptase inhibitors (RTI) in some children. (sun.ac.za)
  • Several informative sites for this distinction are located within or proximal to codons associated with resistance to protease inhibitors or polymerase inhibitors. (biomedcentral.com)
  • This finding providing an explanation for different resistance profiles to protease inhibitors of isolates clustering within cladeI. (biomedcentral.com)
  • Hence, SAMHD1 inhibitors are promising candidates for the sensitisation of leukaemia cells to nucleoside analogue-based therapy. (biomedcentral.com)
  • Remdesivir (GS-5734) is an adenosine analog antiviral drug that inhibits viral RNA polymerase and has demonstrated in vitro activity against various viruses including Ebola, SARS-CoV, and Middle Eastern respiratory syndrome (MERS-CoV). (ccjm.org)
  • Hormonal contraceptives are safe and effective means to avoid unintended pregnancy, but there is concern that coadministration of antiretroviral drugs may alter contraceptive efficacy. (hindawi.com)
  • Although management without VL monitoring has enabled ART rollout, children with virological failure risk developing resistance, which may reduce efficacy of second-line therapy. (prolekare.cz)
  • Seattle, WA, 13 February 2017 - Janssen Sciences Ireland UC (Janssen) announced positive results from the full data read out for two Phase III studies evaluating the safety and efficacy of switching virologically suppressed patients from a three- or four-drug antiretroviral regimen to the two-drug regimen of dolutegravir (ViiV Healthcare) and rilpivirine (Janssen). (jnj.com)
  • Kimberly Smith, M.D., Head of Research & Development at ViiV Healthcare, said: "The TANGO study shows virologically suppressed adults with HIV-1 looking to switch their treatment can get the efficacy of a three-drug TAF-containing regimen with Dovato, a two-drug regimen. (viivhealthcare.com)
  • Authorisation based on GEMINI pivotal trials in which Dovato achieved non-inferior efficacy compared to a dolutegravir-based, three-drug regimen through 48 weeks, with no cases of resistance. (gsk.com)
  • The data from our dolutegravir-based two-drug regimen development programme challenges this, and with the authorisation of Dovato, people living with HIV can for the first time start treatment on a once-daily, single-pill, two-drug regimen with the knowledge that efficacy is non-inferior to a three-drug regimen whilst containing fewer antiretrovirals. (gsk.com)
  • Dolutegravir/rilpivirine maintains the efficacy of a traditional three-drug regimen with only two antiretrovirals. (jnj.com)
  • Those who failed either had some underlying resistance to Rilpivirine at baseline, or had low levels of Rilpivirine at 8 weeks, or had any of the two HIV subtypes (A6/A1). (theseoultimes.com)
  • especially for those subgroups who have one or more factors historically associated with lower response rates to interferon-based therapies (e.g. advanced fibrosis/cirrhosis, high baseline viral concentrations, black race, IL28B non CC genotype, prior null response to peginterferon alfa and ribavirin therapy). (medicines.org.uk)
  • No virus was detectable in plasma from 49.2% of patients, while 42.4% had virological failure (viral load, ≥1000 copies/mL) according to WHO criteria. (scirp.org)
  • The prevalence of transmitted ARVDR in adults was low, as was initial ARVDR in young children (mostly PMTCT-exposed), except for NNRTI resistance in children who had received NVP as part of PMTCT. (sun.ac.za)
  • Drug-induced resistance was found in adults failing first-line NNRTI-based cART, with 83% having resistance to ≥1 drug. (sun.ac.za)
  • In this study, more patients in the emtricitabine and tenofovir arm achieved viral loads below 400 copies/ml after 48 weeks, largely due to fewer discontinuations due to drug side effects. (aidsmap.com)
  • are virally suppressed for at least three months, and are not resistant to either of these drugs and do not have active Hepatitis B (as Cabotegravir cannot treat Hepatitis B, while a Tenofovir disoproxil fumarate (TDF) and Tenofovir Alafenamide (TAF) regimen does). (theseoultimes.com)
  • The development of oral anti-viral treatment with nucleos(t)ide analogues (NAs) has revolutionised the management of chronic hepatitis B (CHB) in the last two decades. (medscape.com)
  • Experiments including photography of fluorescence in HSV-1g or plaque formation by HSV-1f, western blot assays, real-time RT-PCR assays, cytopathic effect inhibition assays, cytotoxicity assays, and viral absorption and penetration assays were performed to explore the antiviral effect and mechanism of the compounds. (molvis.org)
  • Importantly, viral absorption and penetration assays showed that the relative fluorescence intensity of HSV-1g was significantly reduced by SPS in a dose-dependent manner in the absorption test, but no change was observed in the penetration test. (molvis.org)
  • [ 5 ] The goal of ART is to reduce the HIV viral load (RNA PCR) below the level of detection by commercial assays. (medscape.com)
  • These assays detect resistance in fundamentally different ways, although the results generally correlate with each other. (medilib.ir)
  • Inadequate clinical and biological fol- types were determined by phylogenetic tree analysis with low-up has been linked to high rates of drug resistance the Clustal W program ( 8 ). (cdc.gov)
  • INTRODUCTION - The use of drug resistance testing has become an integral part of HIV clinical care. (medilib.ir)
  • A randomized controlled trial of lopinavir/ritonavir demonstrated no apparent clinical or virologic benefit and drug-drug interactions and side effects further limit its utility. (ccjm.org)
  • Those drugs with evidence of clinical activity may also warrant investigation as prevention in high risk populations. (ccjm.org)
  • In 1988 he joined the DuPont Company where he worked both as a bench scientist on HIV drug resistance then designed the clinical trials supporting FDA approval of efavirenz. (stanford.edu)
  • Conclusions Long-term safety profile of nucleoside analogues is now better defined with more data from large real-life cohorts and clinical trials with long-term follow-up. (medscape.com)
  • One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. (unl.pt)
  • Viral supression allows for immunologic improvement (as measured by CD4 counts), prevents the selection of drug-resistance mutation, and decreases HIV transmission to others. (medscape.com)
  • Because of the efavirenz component in this fixed-dose combination, use of many drugs is contraindicated or may require dosing adjustment. (aidsmap.com)
  • The feasibility of incorporating efavirenz (EFV), an antiretroviral agent against HIV into a lipid-based self-emulsifying drug delivery system (SEDDS) containing vegetable oils was investigated. (ru.ac.za)
  • Solutions from the desired optimization function were produced based on desirability and five nanoemulsion formulations were produced and characterized in terms of in vitro release of efavirenz, drug loading capacity, Zeta Potential, droplet sizes and polydispersity index (PDI). (ru.ac.za)
  • Antiviral drugs currently face challenges. (molvis.org)
  • In this discussion of proposed antiviral therapies that may hold some promise against SARS-CoV-2, it should be recognized that antiviral drug development against other RNA respiratory viruses has resulted in very few effective therapies. (ccjm.org)
  • Antiviral drugs do not cure but can control the virus. (msdmanuals.com)
  • This is believed to be due to the lower viral load that is seen in HIV-2 infected patients. (avhandlingar.se)
  • However, why this lower viral load is seen is not known. (avhandlingar.se)
  • A lower viral load means that there are fewer HIV particles in the bloodstream, which can help improve the overall health of the person living with HIV and decrease the likelihood of transmitting the virus to others. (meds4uonline.su)
  • We performed a literature search of PubMed and Ovid databases of articles published between January 1980 and February 2012 to identify English-language reports of drug-drug interactions between hormonal contraceptives (HCs) and antiretroviral drugs (ARVs). (hindawi.com)
  • As access to both modern methods of contraception and antiretroviral drugs (ARVs) expands, women with HIV enter the largely uncharted territory of potential drug interactions. (hindawi.com)
  • We now know more about side effects, drug interactions, drug resistance and how best to use available treatments than ever before. (poz.com)
  • Additionally, Atazanavir has a relatively low risk of drug-drug interactions, making it a suitable option for individuals who may be taking other medications for various health conditions. (meds4uonline.su)
  • We quantify the effects of treatment and estimate the fitness of drug resistant mutants. (plos.org)
  • This finding could provide an explanation of how clinically observed resistant viral mutants may arise. (plos.org)
  • 1 However, little attention has been paid to the potential emergence and spread of drug resistant HIV and its public health implications. (bmj.com)
  • Drug resistant HIV variants selected for during treatment failure (acquired resistance) have the potential to limit the response to subsequent treatment and constitute a reservoir for onward transmission to newly infected individuals (transmitted resistance). (bmj.com)
  • It is therefore important for national HIV treatment programmes to monitor and manage mounting drug resistant HIV. (bmj.com)
  • Until recently, patients developing highly drug-resistant HIV-1 have had limited therapy options. (ucl.ac.uk)
  • Footnote 7 Footnote 8 However, these benefits can be adversely affected by the development of drug-resistant forms of the virus. (canada.ca)
  • The emergence of drug resistance in treated populations (antiretroviral treatment-experienced patients) and transmission of drug- resistant strains to newly infected individuals are important public health concerns in the prevention and control of HIV. (canada.ca)
  • Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus. (aidsmap.com)
  • The fitness of the variant under drug selection (replicative capacity of a resistant variant) may play also a crucial role in the virologic outcome [ 5 ]. (biomedcentral.com)
  • However, the risk varies widely depending on differences in factors such as co-occurrence with other sexually transmitted infections (STIs), level of viral load, stage of disease, and circumcision. (benthamscience.com)
  • Epidemiological and viral characteristics of undiagnosed HIV infections in Botswana. (cdc.gov)
  • Multivariable logistic regression was used to determine the association between specific DRMs and Stanford intermediate-/high-level resistance and factors including REGA subtype, first-line antiretroviral therapy drugs, CD4, and VL at failure. (ox.ac.uk)
  • No patient who experienced virologic failure in either treatment arm developed treatment-emergent resistance also up to week 48. (gsk.com)
  • the predominant reason for failure was poor drug exposure, as detected by measuring lopinavir concentrations in blood plasma and hair samples. (sun.ac.za)
  • Adults failing first-line cART are likely to respond to second-line cART, without failure due to resistance. (sun.ac.za)
  • The lack of cross-resistance between SAMHD1/ DCK substrates and non-substrates provides scope for next-line therapies after treatment failure. (biomedcentral.com)
  • A patient has had a sexual partner on INSTI therapy who was not virologically suppressed or with unknown viral load. (hiv.gov)
  • The participants who failed the regimen developed resistance for both Cabotegravir and Rilpivirine. (theseoultimes.com)
  • The CHMP Positive Opinion follows the US Food and Drug Administration's (FDA) approval of dolutegravir/rilpivirine in November 2017 , [3] and is supported by 48-week data from two pivotal Phase 3 trials (SWORD-1 and SWORD-2) [2] and a pivotal bioequivalence study. (jnj.com)
  • In the setting of transmitted drug resistance, the choice of antiretroviral therapy should be tailored according the the results of resistance (typically genotype) testing. (medscape.com)
  • Among viral factors that may guide the treatment option the most important is the viral infecting genotype. (biomedcentral.com)
  • Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine. (medscape.com)
  • Human immunodeficiency virus evolves rapidly in patients, making the development of drug resistance a major problem in combating the virus. (acs.org)
  • Clinicians who wanted proof that a dolutegravir-based 2-drug-regimen works long-term in treatment-naïve adults with HIV now have evidence to show that it does. (natap.org)
  • [ 9 ] Antiretroviral drug classes and agents within each class are listed in Table 1, below (see individual medication tables for more detail). (medscape.com)
  • Plasma samples were obtained from patients with prior exposure to at least two antiretroviral drug classes and who were on a failing antiretroviral regimen. (scienceopen.com)
  • In practice, the viral load is estimated from the number of copies of ribonucleic acid (RNA) HIV-1 per milliliter of plasma, determined with commercial molecular technic used to evaluate the effectiveness of ART. (scirp.org)
  • 1,000 copies/mL, drug-resistance testing may be unsuccessful but should still be considered. (hiv.gov)
  • At diagnosis, his CD4 count was 276 cells/µL, and his plasma HIV-1 RNA viral load was 193,000 copies/mL. (medscape.com)
  • Surprisingly, target cells with low dNTP/NTP levels may not confer hyper-susceptibility to inhibition, whereas cells with high dNTP/NTP contents are likely to confer natural resistance. (plos.org)
  • Resistance development also changes drug susceptibility distinctly and we show, for the first time, that selection of drug resistance can occur in particular target cells. (plos.org)
  • Furthermore, we examined the effect of co-evolved PR and RT on the susceptibility of patient-derived viruses to INSTIs and viral replicative fitness. (ucl.ac.uk)
  • Results are reported as a fold-change in drug susceptibility of the patient sample compared with a laboratory reference strain without resistance. (medilib.ir)
  • Today's submission takes us a step closer toward offering this option for virologically suppressed adults living with HIV who are looking to treat HIV with fewer drugs. (viivhealthcare.com)
  • Approval of a single pill, two-drug regimen will reduce the number of antiretrovirals virologically suppressed HIV patients have to take and are exposed to in the long-term, representing a true advancement in HIV care," said Dr. Josep M Llibre, Infectious Diseases Dept, University Hospital Germans Trias i Pujol, Badalona, Barcelona. (jnj.com)
  • However, standard clonal analyses and deep sequencing methodologies have confirmed the presence of myriads of mutant genomes in viral populations, and their participation in adaptive processes. (wikipedia.org)
  • 2004 version of the French National Agency for Research low-up and drug supply were irregular and that many on AIDS consensus statements on antiretroviral drug patients interrupted their treatment ( 6 ). (cdc.gov)
  • Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients. (unl.pt)
  • See "Interpretation of HIV drug resistance testing" and "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy" and "Evaluation of the treatment-experienced patient failing HIV therapy" . (medilib.ir)
  • In pediatric patients ages 2-18, the frequency, type, and severity of adverse drug reactions were comparable to those observed in adult subjects, except for rash, which was observed more frequently. (positivelyaware.com)
  • 5 SARS-CoV-2 was isolated from the airway epithelial cells of patients with viral pneumonia in Wuhan. (medsci.org)
  • CNDAC was tested in 13 acute myeloid leukaemia (AML) cell lines, in 26 acute lymphoblastic leukaemia (ALL) cell lines, ten AML sublines adapted to various antileukaemic drugs, 24 single cell-derived clonal AML sublines, and primary leukaemic blasts from 24 AML patients. (biomedcentral.com)
  • It is, however, reassuring from the results of a recent study in a 7-year real-life cohort that no patients discontinued entecavir because of the occurrence of drug-related side effects. (medscape.com)
  • Emerging evidence suggests that they provide a cellular mechanism for induction and emergence of drug resistance and contribute to increased invasive and metastatic potential. (frontiersin.org)
  • I didn't know that nucleoside analog monotherapy-while still the standard of care-wasn't the cutting-edge way to go at the time. (poz.com)
  • Available data suggest that the prevalence of primary drug resistance in Canada is similar to that observed in other developed countries where highly active antiretroviral treatment is widely used. (canada.ca)
  • Although in terms of cost per lives saved HIV treatment is a cost-effective intervention, its sheer cost to the NHS these days is staggering: in London, with a higher HIV prevalence than the rest of the country, 19% of the entire London NHS drugs budget in 2009 was spent on antiretrovirals and 29% of the budget for specialist conditions. (aidsmap.com)