Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome
| العنوان: | Lack of impact of pre-existing T97A HIV-1 integrase mutation on integrase strand transfer inhibitor resistance and treatment outcome |
|---|---|
| المؤلفون: | Kirsten L. White, Michael E. Abram, Renee Ram, Tiffany Barnes, Christian Callebaut, Nicolas A. Margot, Michael D. Miller |
| المصدر: | PLoS ONE PLoS ONE, Vol 12, Iss 2, p e0172206 (2017) |
| بيانات النشر: | Public Library of Science, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, RNA viruses, lcsh:Medicine, HIV Integrase, Quinolones, Pathology and Laboratory Medicine, Raltegravir Potassium, chemistry.chemical_compound, Database and Informatics Methods, Immunodeficiency Viruses, Genotype, Medicine and Health Sciences, Public and Occupational Health, lcsh:Science, Multidisciplinary, biology, Elvitegravir, Antimicrobials, Pharmaceutics, Drugs, Antiretrovirals, Antivirals, Vaccination and Immunization, Integrase, Phenotype, Treatment Outcome, Medical Microbiology, Viral Pathogens, Dolutegravir, Viruses, Pathogens, Sequence Analysis, medicine.drug, Research Article, Bioinformatics, 030106 microbiology, Immunology, Antiretroviral Therapy, Sequence Databases, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Pharmacotherapy, Antibiotic resistance, Drug Therapy, Antiviral Therapy, Microbial Control, Virology, Retroviruses, Drug Resistance, Viral, medicine, Genetics, Humans, HIV Integrase Inhibitors, Codon, Microbial Pathogens, Pharmacology, business.industry, lcsh:R, Lentivirus, Organisms, Biology and Life Sciences, HIV, Raltegravir, Biological Databases, chemistry, Mutation, biology.protein, HIV-1, lcsh:Q, Antimicrobial Resistance, Preventive Medicine, business |
| الوصف: | T97A is an HIV-1 integrase polymorphism associated with integrase strand transfer inhibitor (INSTI) resistance. Using pooled data from 16 clinical studies, we investigated the prevalence of T97A (pre-existing and emergent) and its impact on INSTI susceptibility and treatment response in INSTI-naive patients who enrolled on elvitegravir (EVG)- or raltegravir (RAL)-based regimens. Prior to INSTI-based therapy, primary INSTI resistance-associated mutations (RAMs) were absent and T97A pre-existed infrequently (1.4%; 47 of 3367 integrase sequences); most often among non-B (5.3%) than B (0.9%) HIV-1 subtypes. During INSTI-based therapy, few patients experienced virologic failure with emergent INSTI RAMs (3%; 122 of 3881 patients), among whom T97A emerged infrequently in the presence (n = 6) or absence (n = 8) of primary INSTI RAMs. A comparison between pre-existing and emergent T97A patient populations (i.e., in the absence of primary INSTI RAMs) showed no significant differences in EVG or RAL susceptibility in vitro. Furthermore, among all T97A-containing viruses tested, only 38-44% exhibited reduced susceptibility to EVG and/or RAL (all of low magnitude |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f12f9f93fc86e63cdf1cc4f1cd42126a http://europepmc.org/articles/PMC5315389 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f12f9f93fc86e63cdf1cc4f1cd42126a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|