Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance

Abstract In ART programs in sub-Saharan Africa, a growing proportion of HIV-infected persons initiating first-line antiretroviral therapy (ART) have a history of prior antiretroviral drug use (PAU). We assessed the effect of PAU on the risk of pre-treatment drug resistance (PDR) and virological fail...

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Autores principales:	Seth C. Inzaule, Cissy M. Kityo, Margaret Siwale, Alani Sulaimon Akanmu, Maureen Wellington, Marleen de Jager, Prudence Ive, Kishor Mandaliya, Wendy Stevens, T. Sonia Boender, Pascale Ondoa, Kim C. E. Sigaloff, Denise Naniche, Tobias F. Rinke de Wit, Raph L. Hamers
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Causal Mediation Analysis First-line Empirical Therapy Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Virological Failure (VF) Prevention Of Mother-to-child Transmission (PMTCT) Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0647a6dbb601463f9750fafd510d38ea
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spelling	oai:doaj.org-article:0647a6dbb601463f9750fafd510d38ea2021-12-02T15:09:07ZPrevious antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance10.1038/s41598-018-33538-02045-2322https://doaj.org/article/0647a6dbb601463f9750fafd510d38ea2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33538-0https://doaj.org/toc/2045-2322Abstract In ART programs in sub-Saharan Africa, a growing proportion of HIV-infected persons initiating first-line antiretroviral therapy (ART) have a history of prior antiretroviral drug use (PAU). We assessed the effect of PAU on the risk of pre-treatment drug resistance (PDR) and virological failure (VF) in a multicountry cohort of HIV-infected adults initiated on a standard non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART. Multivariate logistic regression was used to assess the associations between PAU, PDR and VF (defined as viral load ≥400 cps/mL). Causal mediation analysis was used to assess the proportion of the effect of PAU on VF that could be eliminated by intervening on PDR. Of 2737 participants, 122 (4.5%) had a history of PAU. Participants with PAU had a 7.2-fold (95% CI 4.4–11.7) risk of carrying PDR and a 3.1-fold (95% CI 1.6–6.1) increased risk of VF, compared to antiretroviral-naïve participants. Controlling for PDR would eliminate nearly half the effect of PAU on the risk of VF. Patients with a history of PAU are at increased risk of ART failure, which is to a large extent attributable to PDR. These findings support the recent WHO recommendations for use of differentiated, non-NNRTI-based empiric first-line therapy in patients with PAU.Seth C. InzauleCissy M. KityoMargaret SiwaleAlani Sulaimon AkanmuMaureen WellingtonMarleen de JagerPrudence IveKishor MandaliyaWendy StevensT. Sonia BoenderPascale OndoaKim C. E. SigaloffDenise NanicheTobias F. Rinke de WitRaph L. HamersNature PortfolioarticleCausal Mediation AnalysisFirst-line Empirical TherapyNon-nucleoside Reverse Transcriptase Inhibitors (NNRTI)Virological Failure (VF)Prevention Of Mother-to-child Transmission (PMTCT)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-7 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Causal Mediation Analysis First-line Empirical Therapy Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Virological Failure (VF) Prevention Of Mother-to-child Transmission (PMTCT) Medicine R Science Q
spellingShingle	Causal Mediation Analysis First-line Empirical Therapy Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) Virological Failure (VF) Prevention Of Mother-to-child Transmission (PMTCT) Medicine R Science Q Seth C. Inzaule Cissy M. Kityo Margaret Siwale Alani Sulaimon Akanmu Maureen Wellington Marleen de Jager Prudence Ive Kishor Mandaliya Wendy Stevens T. Sonia Boender Pascale Ondoa Kim C. E. Sigaloff Denise Naniche Tobias F. Rinke de Wit Raph L. Hamers Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance
description	Abstract In ART programs in sub-Saharan Africa, a growing proportion of HIV-infected persons initiating first-line antiretroviral therapy (ART) have a history of prior antiretroviral drug use (PAU). We assessed the effect of PAU on the risk of pre-treatment drug resistance (PDR) and virological failure (VF) in a multicountry cohort of HIV-infected adults initiated on a standard non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART. Multivariate logistic regression was used to assess the associations between PAU, PDR and VF (defined as viral load ≥400 cps/mL). Causal mediation analysis was used to assess the proportion of the effect of PAU on VF that could be eliminated by intervening on PDR. Of 2737 participants, 122 (4.5%) had a history of PAU. Participants with PAU had a 7.2-fold (95% CI 4.4–11.7) risk of carrying PDR and a 3.1-fold (95% CI 1.6–6.1) increased risk of VF, compared to antiretroviral-naïve participants. Controlling for PDR would eliminate nearly half the effect of PAU on the risk of VF. Patients with a history of PAU are at increased risk of ART failure, which is to a large extent attributable to PDR. These findings support the recent WHO recommendations for use of differentiated, non-NNRTI-based empiric first-line therapy in patients with PAU.
format	article
author	Seth C. Inzaule Cissy M. Kityo Margaret Siwale Alani Sulaimon Akanmu Maureen Wellington Marleen de Jager Prudence Ive Kishor Mandaliya Wendy Stevens T. Sonia Boender Pascale Ondoa Kim C. E. Sigaloff Denise Naniche Tobias F. Rinke de Wit Raph L. Hamers
author_facet	Seth C. Inzaule Cissy M. Kityo Margaret Siwale Alani Sulaimon Akanmu Maureen Wellington Marleen de Jager Prudence Ive Kishor Mandaliya Wendy Stevens T. Sonia Boender Pascale Ondoa Kim C. E. Sigaloff Denise Naniche Tobias F. Rinke de Wit Raph L. Hamers
author_sort	Seth C. Inzaule
title	Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance
title_short	Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance
title_full	Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance
title_fullStr	Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance
title_full_unstemmed	Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance
title_sort	previous antiretroviral drug use compromises standard first-line hiv therapy and is mediated through drug-resistance
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/0647a6dbb601463f9750fafd510d38ea
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Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance

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