دورية أكاديمية
أعرض في EDS

Presence, persistence and effects of pre-treatment HIV-1 drug resistance variants detected using next generation sequencing: A Retrospective longitudinal study from rural coastal Kenya.

التفاصيل البيبلوغرافية
العنوان: Presence, persistence and effects of pre-treatment HIV-1 drug resistance variants detected using next generation sequencing: A Retrospective longitudinal study from rural coastal Kenya.
المؤلفون: Hassan AS; KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya., Bibby DF; Virus Reference Department, Public Health England, London, United Kingdom., Mwaringa SM; KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya., Agutu CA; KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya., Ndirangu KK; Kilifi County Hospital, Kilifi, Kenya., Sanders EJ; KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.; Centre for Tropical Medicine & Global Health, University of Oxford, Oxford, United Kingdom., Cane PA; Virus Reference Department, Public Health England, London, United Kingdom., Mbisa JL; Virus Reference Department, Public Health England, London, United Kingdom., Berkley JA; KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya.; Centre for Tropical Medicine & Global Health, University of Oxford, Oxford, United Kingdom.
المصدر: PloS one [PLoS One] 2019 Feb 13; Vol. 14 (2), pp. e0210559. Date of Electronic Publication: 2019 Feb 13 (Print Publication: 2019).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Antiretroviral Therapy, Highly Active*/methods , Drug Resistance, Viral*, Anti-Retroviral Agents/*therapeutic use , HIV Infections/*drug therapy , HIV-1/*drug effects, Adult ; Anti-Retroviral Agents/pharmacology ; Female ; Genetic Variation/drug effects ; HIV Infections/epidemiology ; HIV Infections/virology ; HIV-1/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Kenya/epidemiology ; Longitudinal Studies ; Male ; Phylogeny ; Retrospective Studies ; Rural Population ; Young Adult
مستخلص: Background: The epidemiology of HIV-1 drug resistance (HIVDR) determined by Sanger capillary sequencing, has been widely studied. However, much less is known about HIVDR detected using next generation sequencing (NGS) methods. We aimed to determine the presence, persistence and effect of pre-treatment HIVDR variants detected using NGS in HIV-1 infected antiretroviral treatment (ART) naïve participants from rural Coastal Kenya.
Methods: In a retrospective longitudinal study, samples from HIV-1 infected participants collected prior [n = 2 time-points] and after [n = 1 time-point] ART initiation were considered. An ultra-deep amplicon-based NGS assay, calling for nucleotide variants at >2.0% frequency of viral population, was used. Suspected virologic failure (sVF) was defined as a one-off HIV-1 viral load of >1000 copies/ml whilst on ART.
Results: Of the 50 eligible participants, 12 (24.0% [95% CI: 13.1-38.2]) had at least one detectable pre-treatment HIVDR variant against Protease Inhibitors (PIs, n = 6 [12%]), Nucleoside Reverse Transcriptase Inhibitors (NRTIs, n = 4 [8.0%]) and Non-NRTIs (n = 3 [6.0%]). Overall, 15 pre-treatment resistance variants were detected (frequency, range: 2.3-92.0%). A positive correlation was observed between mutation frequency and absolute load for NRTI and/or NNRTI variants (r = 0.761 [p = 0.028]), but not for PI variants (r = -0.117 [p = 0.803]). Participants with pre-treatment NRTI and/or NNRTI resistance had increased odds of sVF (OR = 6.0; 95% CI = 1.0-36.9; p = 0.054).
Conclusions: Using NGS, pre-treatment resistance variants were common, though observed PI variants were unlikely transmitted, but rather probably generated de novo. Even when detected from a low frequency, pre-treatment NRTI and/or NNRTI resistance variants may adversely affect treatment outcomes.
Competing Interests: The authors have declared that no competing interests exist.
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معلومات مُعتمدة: WT089351MA United Kingdom WT_ Wellcome Trust; WT083579MA United Kingdom WT_ Wellcome Trust; 107752/Z/15/Z United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; 209294/Z/17/Z United Kingdom WT_ Wellcome Trust
المشرفين على المادة: 0 (Anti-Retroviral Agents)
تواريخ الأحداث: Date Created: 20190214 Date Completed: 20191030 Latest Revision: 20231006
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6373901
DOI: 10.1371/journal.pone.0210559
PMID: 30759103
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0210559