Abstract Introduction Viral suppression estimates are essential for monitoring the performance of HIV programmes. South Africa introduced dolutegravir (DTG)‐based antiretroviral therapy (ART) in 2019. We sought to generate updated estimates of viral suppression in South African adults on ART and investigate predictors of viral non‐suppression. Methods This retrospective cohort study used data from seven South African cohorts participating in the International epidemiology Databases to Evaluate AIDS collaboration. Three main analyses were performed using a viral suppression threshold of 1000 HIV RNA copies/ml. In the first analysis, we fitted a logistic regression model using the full data from the study period (2005−2023). Then, in two causal analyses, we used logistic regression with inverse probability weighting to assess the effects of starting ART on DTG‐based regimens (as opposed to starting on non‐DTG‐based ART) and switching to DTG while virally suppressed (compared to remaining on non‐DTG‐based ART). In sensitivity analyses, we reduced the suppression threshold to 400 copies/ml and excluded those with missing baseline CD4+ cell count measurements. Results There were 380,720 participants contributing 2,090,912 person‐years of observation. Most participants were female (64.7%), and the median age at ART initiation was 35.0 years (interquartile range 28.9−42.3). Viral suppression increased over time, reaching 95.9% in 2023. Twenty‐one percent of participants either started ART on DTG‐based regimens (7.1%) or switched to DTG‐based regimens from a virally suppressed state (14.0%). DTG‐based ART was protective against viral non‐suppression in both causal models, with adjusted odds ratios of 0.54 (95% confidence interval CI 0.48−0.61) and 0.36 (95% CI 0.32−0.39) for those initiating ART on DTG and those switching to DTG, respectively. A history of ART interruption was strongly associated with viral non‐suppression, with adjusted odds ratios ranging from 2.49 to 4.55. The odds of non‐suppression decreased with increasing age, increasing duration on ART and increasing baseline CD4+ cell count. Results were consistent across sensitivity analyses. Conclusions DTG‐based regimens improve viral suppression among both ART‐naïve individuals and those transitioning while suppressed. ART interruptions pose a risk to the sustained success of ART programmes and may further impede efforts to recover from the impacts of recent funding cuts.
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