Resistance to Dolutegravir in Treatment-experienced Patients in South Africa: A Retrospective Cohort Study.

Background: Dolutegravir resistance has been reported more frequently in patients with prior treatment experience compared to those on dolutegravir in first-line antiretroviral therapy (ART). The widespread use of dolutegravir in resource-limited programmatic settings might facilitate the emergence of resistance. Data on the prevalence of dolutegravir resistance from programmatic settings in Africa are scarce.

Methods: This retrospective observational cohort study assessed dolutegravir resistance in routine care settings of the Western Cape provincial public healthcare sector program between February 2021 and June 2024. Treatment-experienced adults who developed virologic failure (two HIV-1 RNA ≥1000 copies/mL), who had received dolutegravir-based ART for >24 months, were eligible for genotypic antiretroviral resistance testing (GART). Drug resistance mutations (DRMs) and resistance levels were classified using the Stanford database.

Results: Among 99 eligible patients, 76 had GART performed, and 68 had successful sequences. Among these 68, 43 (63%) had dolutegravir DRMs with: 1 potential low, 1 low, 15 intermediate, and 26 high resistance levels. The median time on dolutegravir-based ART was 24 months (IQR, 23-31). Of the 43 patients with dolutegravir DRMs, 21 (49%) were receiving zidovudine-lamivudine-dolutegravir and 19 (44%) were receiving tenofovir-lamivudine-dolutegravir; 42/43 had prior ART experience.

Conclusions: Over 60% of patients with prior treatment experience who had been on dolutegravir-based ART for over two years and experienced virologic failure had intermediate or high level dolutegravir resistance. This suggests that criteria for GART used are too stringent, which has resource implications in programmatic settings where access to resistance testing for individual management is limited.