Background: Clinical trials evaluating the impact of switching to dolutegravir have excluded individuals with poorly controlled viremia. However, in practice, clinicians may switch individuals to dolutegravir who have such challenges. Utilizing the Target Trial Framework, we estimated the effect of switching to a dolutegravir-based regimen, vs not switching and remaining on an efavirenz-based regimen, on 12- and 24-month retention and viral suppression in Johannesburg, South Africa, from 2019 to 2022. Methods: Using data from the Themba Lethu HIV Clinical Cohort, individuals were eligible if they were currently on an efavirenz-based regimen, aged 16+, and not pregnant at the start of each trial. We conducted a pooled linear regression model with bootstrapping to estimate the causal risk difference and 95% CI adjusting for patient characteristics via inverse probability treatment weighting. Results: Of 1493 individuals, 967 (64.7%) switched to a dolutegravir-based regimen over 9 sequential trials, and 526 (35.2%) did not. At 12 months, switch to a dolutegravir-based regimen was associated with a 14 percentage point (95% CI, 0.10 to 0.19) increase in retention and a 2 percentage point (95% CI, -0.04 to 0.08) increase in viral suppression. By 24 months, we observed a 1 percentage point (95% CI, -0.05 to 0.07) increase in retention and an 8 percentage point (95% CI, 0.02 to 0.14) increase in viral suppression. Conclusions: Switching to dolutegravir was associated with a 14 percentage point increase in retention at 12 months and an 8 percentage point increase in viral suppression at 24 months. Our findings suggest that switching to dolutegravir does not harm and might improve retention and viral suppression over a 24-month period.
Zheng et al. (2026) studied this question.