An apparent paradox: resistance mutations in HIV-1 DNA predict improved virological responses to antiretroviral therapy

Geretti, Anna Maria ORCID: 0000-0002-3670-6588, Abdullahi, Adam ORCID: 0000-0001-9703-8264, Fopoussi, Olga Mafotsing, Bonnett, Laura ORCID: 0000-0002-6981-9212, Defo, Victoire Fokom, Moudourou, Sylvie, Fokam, Joseph, Kouanfack, Charles and Torimiro, Judith (2019) An apparent paradox: resistance mutations in HIV-1 DNA predict improved virological responses to antiretroviral therapy. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 74 (10). pp. 3011-3015.

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Abstract

<h4>Background</h4>In sub-Saharan Africa, detecting resistance-associated mutations (RAMs) at failure of first-line ART with two NRTIs plus an NNRTI predicts improved virological responses to second-line therapy with two NRTIs plus a ritonavir-boosted PI (PI/r). This indicates residual NRTI activity in the presence of RAMs, although additional factors may contribute to the effect.<h4>Objectives</h4>The aim of this study was to investigate the influence of pre-existing RAMs on the outcomes of maintenance monotherapy with ritonavir-boosted darunavir within a randomized trial in Cameroon.<h4>Methods</h4>RAMs were detected in HIV-1 DNA using PBMCs collected at initiation of darunavir/ritonavir monotherapy. Adherence was assessed by pill count and visual analogue scale (VAS). Predictors of virological failure (confirmed or last available viral load >400 copies/mL) were explored by logistic regression analysis. Trial name = MANET (NCT02155101).<h4>Results</h4>After NNRTI-based therapy, participants (n = 81) had received PI/r-based therapy for a median of 3.2 years and had a confirmed viral load <60 copies/mL and a median CD4 count of 466 cells/mm3. NRTI and NNRTI RAMs were detected in 39/60 (65.0%) and 41/60 (68.3%) HIV-1 DNA sequences, respectively. Over 48 weeks of monotherapy, 16/81 (19.8%) patients experienced virological failure. After adjusting for age, HIV-1 DNA load, adherence by VAS and RAM status, virological failure was less likely with higher VAS-measured adherence (adjusted OR 0.04, 95% CI 0.01-0.37; P = 0.004) and detectable HIV-1 DNA RAMs (adjusted OR 0.15, 95% CI 0.03-0.82; P = 0.028).<h4>Conclusions</h4>Pre-existing NRTI and NNRTI RAMs are associated with improved virological responses to NRTI-sparing ART in sub-Saharan Africa, indicating a predictive effect that is independent of residual NRTI activity.

Item Type:	Article
Uncontrolled Keywords:	Humans, HIV-1, HIV Infections, Ritonavir, DNA, Viral, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Drug Therapy, Combination, Antiretroviral Therapy, Highly Active, Viral Load, Drug Resistance, Viral, Mutation, Adult, Middle Aged, Cameroon, Female, Male, Darunavir
Depositing User:	Symplectic Admin
Date Deposited:	27 Apr 2020 10:12
Last Modified:	19 Jan 2023 00:08
DOI:	10.1093/jac/dkz264
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3071007