Dolutegravir Resistance in Mozambique: Insights from a Programmatic HIV Resistance Testing Intervention in a Highly ART Experienced Cohort

Background: Treatment failure continues to play a role in HIV-related morbidity in Mozambique. ART regimen switch is 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 Centre, 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 December 2020 and February 2024 was conducted to guide future program enhancements. 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 probability 95%. Results: Total of 106 persons underwent HIV-GT, 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 3 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). The mean relative DTG-R score (the DTG-R score standardized by total number of INSTI mutations) was 20.6 (95% CrI: 19, 22.2). The relative DTG-R score was positively correlated with the number of major mutations (bootstrapped Pearson’s correlation coefficient, r: 0.61 [95% CrI: 0.42, 0.77; pd: 100%]). None of people on a protease inhibitor regimen had any INSTI mutation. Conclusions: In contexts with limited access to genotyping 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 capacity for identifying PLWH with resistant mutations to dolutegravir (DTG), thereby allowing the continuation of the effective DTG regimen without unnecessary regimen switches.