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

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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number15751
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Cite this

Inzaule, S. C., Kityo, C. M., Siwale, M., Akanmu, A. S., Wellington, M., de Jager, M., ... Hamers, R. L. (2018). Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance. Scientific Reports, 8(1), [15751]. https://doi.org/10.1038/s41598-018-33538-0
Inzaule, Seth C. ; Kityo, Cissy M. ; Siwale, Margaret ; Akanmu, Alani Sulaimon ; Wellington, Maureen ; de Jager, Marleen ; Ive, Prudence ; Mandaliya, Kishor ; Stevens, Wendy ; Boender, T. Sonia ; Ondoa, Pascale ; Sigaloff, Kim C.E. ; Naniche, Denise ; Rinke de Wit, Tobias F. ; Hamers, Raph L. / Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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title = "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 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-na{\"i}ve 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.",
author = "Inzaule, {Seth C.} and Kityo, {Cissy M.} and Margaret Siwale and Akanmu, {Alani Sulaimon} and Maureen Wellington and {de Jager}, Marleen and Prudence Ive and Kishor Mandaliya and Wendy Stevens and Boender, {T. Sonia} and Pascale Ondoa and Sigaloff, {Kim C.E.} and Denise Naniche and {Rinke de Wit}, {Tobias F.} and Hamers, {Raph L.}",
year = "2018",
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doi = "10.1038/s41598-018-33538-0",
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Inzaule, SC, Kityo, CM, Siwale, M, Akanmu, AS, Wellington, M, de Jager, M, Ive, P, Mandaliya, K, Stevens, W, Boender, TS, Ondoa, P, Sigaloff, KCE, Naniche, D, Rinke de Wit, TF & Hamers, RL 2018, 'Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance' Scientific Reports, vol. 8, no. 1, 15751. https://doi.org/10.1038/s41598-018-33538-0

Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance. / Inzaule, Seth C.; Kityo, Cissy M.; Siwale, Margaret; Akanmu, Alani Sulaimon; Wellington, Maureen; de Jager, Marleen; Ive, Prudence; Mandaliya, Kishor; Stevens, Wendy; Boender, T. Sonia; Ondoa, Pascale; Sigaloff, Kim C.E.; Naniche, Denise; Rinke de Wit, Tobias F.; Hamers, Raph L.

In: Scientific Reports, Vol. 8, No. 1, 15751, 01.12.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Previous antiretroviral drug use compromises standard first-line HIV therapy and is mediated through drug-resistance

AU - Inzaule, Seth C.

AU - Kityo, Cissy M.

AU - Siwale, Margaret

AU - Akanmu, Alani Sulaimon

AU - Wellington, Maureen

AU - de Jager, Marleen

AU - Ive, Prudence

AU - Mandaliya, Kishor

AU - Stevens, Wendy

AU - Boender, T. Sonia

AU - Ondoa, Pascale

AU - Sigaloff, Kim C.E.

AU - Naniche, Denise

AU - Rinke de Wit, Tobias F.

AU - Hamers, Raph L.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41598-018-33538-0

DO - 10.1038/s41598-018-33538-0

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