HIV Dolutegravir resistance and multiclass failure in Mozambique: findings from a real-world cohort

Abstract

Background: Dolutegravir (DTG) is the anchor drug of the first-line agent for HIV treatment globally, including low- and middle-income countries. Although clinical trials report low rates of integrase inhibitor resistance, real-world data from sub-Saharan Africa suggest a different scenario. We aimed to assess the prevalence and patterns of DTG resistance in Mozambique, building on prior preliminary findings with an expanded cohort and extended observation period. Methods: We conducted a retrospective observational study in five DREAM centers in Mozambique. HIV-positive individuals on DTG-based antiretroviral therapy (ART) with confirmed virological failure (HIV RNA > 1000 copies/mL) between July 2022 and December 2024 were included. Participants underwent genotypic resistance testing after six months of enhanced adherence support. Resistance mutations were identified via Sanger sequencing and interpreted using the Stanford HIV Drug Resistance Database. Results: Of 28 individual tested, 13 (46.4%) exhibited DTG resistance (12/13 with intermediate or high-level resistance); 92.3% harboured HIV-1 subtype C. Frequently observed mutations included G118R (43.8%), E138K (43.8%), L74M (31.3%), and R263K (25.0%), often in combination. All DTG-resistant individuals who underwent testing for other drug classes (n = 9) also showed co-resistance to NRTIs and/or NNRTIs. Notably, high-level resistance emerged also in 6 failing participants having shifted to DTG while virologically suppressed. Conclusions: This study reports the presence of DTG resistance and multiclass failure in Mozambique, suggesting potential limitations of current strategies. Sentinel surveillance and expanded access to resistance testing are important to preserve the efficacy of DTG-based regimens and inform future deployment of long-acting therapies in sub-Saharan Africa.