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

Geretti, Anna Maria, Abdullahi, Adam, Fopoussi, Olga Mafotsing, Bonnett, Laura, 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:	15 Jun 2024 01:47
DOI:	10.1093/jac/dkz264
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3071007