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Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya

HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey co...

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Autores principales: Onywera, Harris, Maman, David, Inzaule, Seth, Auma, Erick, Were, Kennedy, Fredrick, Harrison, Owiti, Prestone, Opollo, Valarie, Etard, Jean-François, Mukui, Irene, Kim, Andrea A., Zeh, Clement
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298248/
https://www.ncbi.nlm.nih.gov/pubmed/28178281
http://dx.doi.org/10.1371/journal.pone.0171124
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author Onywera, Harris
Maman, David
Inzaule, Seth
Auma, Erick
Were, Kennedy
Fredrick, Harrison
Owiti, Prestone
Opollo, Valarie
Etard, Jean-François
Mukui, Irene
Kim, Andrea A.
Zeh, Clement
author_facet Onywera, Harris
Maman, David
Inzaule, Seth
Auma, Erick
Were, Kennedy
Fredrick, Harrison
Owiti, Prestone
Opollo, Valarie
Etard, Jean-François
Mukui, Irene
Kim, Andrea A.
Zeh, Clement
author_sort Onywera, Harris
collection PubMed
description HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15–59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7–17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8–11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2–14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2–6.2) for protease inhibitors. Three (3.4% 95% CI 0.8–10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.
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spelling pubmed-52982482017-02-17 Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya Onywera, Harris Maman, David Inzaule, Seth Auma, Erick Were, Kennedy Fredrick, Harrison Owiti, Prestone Opollo, Valarie Etard, Jean-François Mukui, Irene Kim, Andrea A. Zeh, Clement PLoS One Research Article HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15–59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7–17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8–11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2–14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2–6.2) for protease inhibitors. Three (3.4% 95% CI 0.8–10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions. Public Library of Science 2017-02-08 /pmc/articles/PMC5298248/ /pubmed/28178281 http://dx.doi.org/10.1371/journal.pone.0171124 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Onywera, Harris
Maman, David
Inzaule, Seth
Auma, Erick
Were, Kennedy
Fredrick, Harrison
Owiti, Prestone
Opollo, Valarie
Etard, Jean-François
Mukui, Irene
Kim, Andrea A.
Zeh, Clement
Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya
title Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya
title_full Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya
title_fullStr Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya
title_full_unstemmed Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya
title_short Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya
title_sort surveillance of hiv-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western kenya
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298248/
https://www.ncbi.nlm.nih.gov/pubmed/28178281
http://dx.doi.org/10.1371/journal.pone.0171124
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