Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa

Limited availability of viral load (VL) monitoring in HIV treatment programmes in sub-Saharan Africa can delay switching to second-line ART, leading to the accumulation of drug resistance mutations (DRMs). The objective of this study was to evaluate the accumulation of resistance to reverse transcri...

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Published in:Journal of antimicrobial chemotherapy 2016-10, Vol.71 (10), p.2918-2927
Main Authors: Boender, T Sonia, Kityo, Cissy M, Boerma, Ragna S, Hamers, Raph L, Ondoa, Pascale, Wellington, Maureen, Siwale, Margaret, Nankya, Immaculate, Kaudha, Elizabeth, Akanmu, Alani Sulaimon, Botes, Mariette E, Steegen, Kim, Calis, Job C J, Rinke de Wit, Tobias F, Sigaloff, Kim C E
Format: Article
Language:English
Subjects:
Adolescent
Adult
Africa South of the Sahara - epidemiology
Anti-HIV Agents - administration & dosage
Anti-HIV Agents - adverse effects
Anti-HIV Agents - therapeutic use
Antiretroviral Therapy, Highly Active - adverse effects
Child
Child, Preschool
Drug Resistance, Viral - genetics
Female
HIV Infections - drug therapy
HIV Infections - epidemiology
HIV Infections - virology
HIV-1 - drug effects
HIV-1 - genetics
HIV-1 - isolation & purification
Humans
Male
Mutation
Retrospective Studies
Reverse Transcriptase Inhibitors - administration & dosage
Reverse Transcriptase Inhibitors - adverse effects
Reverse Transcriptase Inhibitors - therapeutic use
Treatment Failure
Viral Load - drug effects
Young Adult
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cited_by cdi_FETCH-LOGICAL-c389t-b90e6c3f8e842bf09831c050f1b236b213b894fbec67de642ff1fc3a5ffd7d073
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creator Boender, T Sonia
Kityo, Cissy M
Boerma, Ragna S
Hamers, Raph L
Ondoa, Pascale
Wellington, Maureen
Siwale, Margaret
Nankya, Immaculate
Kaudha, Elizabeth
Akanmu, Alani Sulaimon
Botes, Mariette E
Steegen, Kim
Calis, Job C J
Rinke de Wit, Tobias F
Sigaloff, Kim C E
description Limited availability of viral load (VL) monitoring in HIV treatment programmes in sub-Saharan Africa can delay switching to second-line ART, leading to the accumulation of drug resistance mutations (DRMs). The objective of this study was to evaluate the accumulation of resistance to reverse transcriptase inhibitors after continued virological failure on first-line ART, among adults and children in sub-Saharan Africa. HIV-1-positive adults and children on an NNRTI-based first-line ART were included. Retrospective VL and, if VL ≥1000 copies/mL, pol genotypic testing was performed. Among participants with continued virological failure (≥2 VL ≥1000 copies/mL), drug resistance was evaluated. At first virological failure, DRM(s) were detected in 87% of participants: K103N (38.7%), G190A (21.8%), Y181C (20.2%), V106M (8.4%), K101E (8.4%), any E138 (7.6%) and V108I (7.6%) associated with NNRTIs, and M184V (69.7%), any thymidine analogue mutation (9.2%), K65R (5.9%) and K70R (5.0%) associated with NRTIs. New DRMs accumulated with an average rate of 1.45 (SD 2.07) DRM per year; 0.62 (SD 1.11) NNRTI DRMs and 0.84 (SD 1.38) NRTI DRMs per year, respectively. The predicted susceptibility declined significantly after continued virological failure for all reverse transcriptase inhibitors (all P 
doi_str_mv 10.1093/jac/dkw218
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The objective of this study was to evaluate the accumulation of resistance to reverse transcriptase inhibitors after continued virological failure on first-line ART, among adults and children in sub-Saharan Africa. HIV-1-positive adults and children on an NNRTI-based first-line ART were included. Retrospective VL and, if VL ≥1000 copies/mL, pol genotypic testing was performed. Among participants with continued virological failure (≥2 VL ≥1000 copies/mL), drug resistance was evaluated. At first virological failure, DRM(s) were detected in 87% of participants: K103N (38.7%), G190A (21.8%), Y181C (20.2%), V106M (8.4%), K101E (8.4%), any E138 (7.6%) and V108I (7.6%) associated with NNRTIs, and M184V (69.7%), any thymidine analogue mutation (9.2%), K65R (5.9%) and K70R (5.0%) associated with NRTIs. New DRMs accumulated with an average rate of 1.45 (SD 2.07) DRM per year; 0.62 (SD 1.11) NNRTI DRMs and 0.84 (SD 1.38) NRTI DRMs per year, respectively. The predicted susceptibility declined significantly after continued virological failure for all reverse transcriptase inhibitors (all P &lt; 0.001). Acquired drug resistance patterns were similar in adults and children. Patterns of drug resistance after virological failure on first-line ART are similar in adults and children in sub-Saharan Africa. 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The predicted susceptibility declined significantly after continued virological failure for all reverse transcriptase inhibitors (all P &lt; 0.001). Acquired drug resistance patterns were similar in adults and children. Patterns of drug resistance after virological failure on first-line ART are similar in adults and children in sub-Saharan Africa. Improved VL monitoring to prevent accumulation of mutations, and new drug classes to construct fully active regimens, are required.</abstract><cop>England</cop><pmid>27342546</pmid><doi>10.1093/jac/dkw218</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Africa South of the Sahara - epidemiology
Anti-HIV Agents - administration & dosage
Anti-HIV Agents - adverse effects
Anti-HIV Agents - therapeutic use
Antiretroviral Therapy, Highly Active - adverse effects
Child
Child, Preschool
Drug Resistance, Viral - genetics
Female
HIV Infections - drug therapy
HIV Infections - epidemiology
HIV Infections - virology
HIV-1 - drug effects
HIV-1 - genetics
HIV-1 - isolation & purification
Humans
Male
Mutation
Retrospective Studies
Reverse Transcriptase Inhibitors - administration & dosage
Reverse Transcriptase Inhibitors - adverse effects
Reverse Transcriptase Inhibitors - therapeutic use
Treatment Failure
Viral Load - drug effects
Young Adult
title Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa
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