Dolutegravir Resistance in Mozambique: Insights from a Programmatic HIV Resistance Testing Intervention in a Highly Antiretroviral Therapy-Experienced Cohort

TL;DR

A study in Mozambique finds high dolutegravir resistance among HIV patients, suggesting adherence strategies can help avoid unnecessary treatment changes.

Contribution

The study introduces an algorithm combining adherence reinforcement and supervised ART to predict and manage dolutegravir resistance in resource-limited settings.

Findings

89.5% of patients on dolutegravir-based regimens had confirmed resistance mutations.

Common mutations included G118R, R263K, and Q148RK in the integrase gene.

The proposed algorithm effectively identified resistance without unnecessary regimen switches.

Abstract

Background: Treatment failure continues to play a role in HIV-related morbidity in Mozambique. Antiretroviral therapy (ART) regimen switches are decided empirically, as HIV genotypic resistance testing (HIV-GT) is unavailable in Mozambique’s public health system. Since 2016, Médecins Sans Frontières (MSF) and I-TECH have provided access to HIV-GT at Alto Maé Health Center, Maputo. We describe the cohort of people with virologic failure (VF) that underwent HIV-GT and analyze dolutegravir (DTG) resistance (R) patterns. Methods: This cross-sectional assessment of routine programmatic data between July 2020 and February 2024 was conducted to guide future program enhancements. People living with HIV (PLWH) receiving ART beyond the first line with confirmed VF were included. Mutations were interpreted according to the Stanford HIVdb algorithm. We applied Bayesian bootstrapping for analysis, and the threshold for significance of effects was defined as a probability of 95%. Results: A total of 106 persons underwent HIV-GT following a structured adherence strategy, 62 (58.5%) of whom were on a DTG-based regimen. Fifty-seven of the 62 samples from persons on a DTG-based regimen were sequenced, and 51 (89.5% [95% CrI: 80.7, 96.2]) had confirmed resistance to DTG; the mean DTG-R score was 70.2 (95% CrI: 62.2, 78). Samples with DTG-R had a median of three INSTI mutations (IQR 1–4). Major DTG-associated mutations were found in 46 out of 57 samples: G118R (n = 28), R263K (n = 15), and Q148RK (n = 7). None of the people on the protease inhibitor regimen had an INSTI mutation. Conclusions: In contexts with limited access to resistance testing, the introduction of algorithms to identify PLWH at risk of developing drug resistance is strongly recommended. The proposed algorithm incorporates adherence reinforcement strategies, as recommended in national policies, followed by a short, supervised antiretroviral therapy (ART) support strategy. This approach has shown a high predictive value for identifying PLWH with resistance mutations to dolutegravir (DTG), thereby allowing the continuation of the effective DTG regimen without unnecessary regimen switches.

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