Initiation of dolutegravir vs. efavirenz on 12- and 24-month retention and viral suppression: a target trial emulation

Background South Africa's antiretroviral therapy (ART) treatment guidelines in 2019 were revised to use dolutegravir as part of first-line ART instead of efavirenz due to recommendations from the World Health Organization and findings from clinical trials indicating noninferior efficacy and reduced side effects. Utilizing the target trial framework, we estimated the effect of initiating a dolutegravir-based regimen compared to an efavirenz-based regimen among treatment-naïve people living with HIV initiating treatment in Johannesburg, South Africa from 2019 to 2022 on retention and viral suppression. Methods We used linear regression to estimate causal risk differences on 12- and 24-month retention and viral suppression. Characteristics of those who initiated dolutegravir vs. efavirenz were balanced through inverse probability of treatment weighting. The covariates included: natal sex, age, year of initiation, education level, employment status, tuberculosis, WHO stage, smoking and alcohol use. Results Of the 2930 individuals initiating ART, 1847 initiated a dolutegravir-based regimen and 1083 initiated an efavirenz-based regimen. The median age was 45.1 years (IQR: 37.1, 53.0). Initiation of dolutegravir was associated with a 5-percentage point increase (95% confidence interval (CI): -0.02, 0.11) in retention and 4-percentage point increase (95% CI: -0.06, 0.16) in viral suppression at 12 months. At 24 months, dolutegravir was associated with a 10-percentage point (95% CI: 0.03, 0.16) increase in retention and a 14-percentage point (95% CI: -0.02, 0.30) increase in viral suppression. Conclusions Initiation of dolutegravir led to an appreciable increase in retention and viral suppression over 24 months when compared to efavirenz. Dolutegravir may lead to increases in long-term retention.