South Africa Achieves 96% HIV Viral Suppression with Dolutegravir-Based Therapies
A large South African cohort study of over 380,000 adults living with HIV confirms the superior effectiveness of dolutegravir-based regimens in achieving viral suppression, while also highlighting the detrimental impact of interruptions to antiretroviral treatment. Viral suppression reached 95.9% in 2023, exceeding the 95% target set by UNAIDS.
Dolutegravir’s Impact in South Africa
South Africa has the world’s largest antiretroviral treatment (ART) program. Since the introduction of dolutegravir (DTG) in November 2019 as a recommended first-line treatment, questions remained regarding its real-world impact. This was particularly relevant given the disruptions to HIV care caused by the COVID-19 pandemic.
A team of South African and international researchers, coordinated by Haroon Moolla (University of Cape Town), analyzed data from seven cohorts within the IeDEA-Southern Africa collaboration, covering the period 2005-2023. The findings were published in January 2026 in the Journal of the International AIDS Society.
Large-Scale Cohort Study
The study included 380,720 adults who initiated ART between 2005 and 2023, totaling over 2 million person-years of follow-up. The population was predominantly female (64.7%), with a median age of 35 years and a median CD4 count of 236 cells/mm³ at treatment initiation. Approximately one-fifth of participants (21.1%) either started treatment with DTG (7.1%) or switched to a DTG-based combination while virally suppressed (14.0%). Notably, 38.2% of participants experienced at least one treatment interruption, with a median duration of 103 days.
Three statistical models were used to assess the determinants of viral non-suppression (threshold of 1000 copies/ml). Two causal analyses, using inverse probability weighting, demonstrated a substantial protective effect of DTG. Individuals initiating treatment with DTG compared to those starting other regimens had an adjusted odds ratio (aOR) of viral non-suppression of 0.54 (95% CI: 0.48-0.61), representing a nearly 50% reduction in the risk of virological failure. The effect was even more pronounced in those who switched to DTG from a virally suppressed state, with an aOR of 0.36 (95% CI: 0.32-0.39).
Treatment Interruptions: A Major Risk Factor
The most striking finding of the study concerns the impact of ART interruptions. Participants with a history of interruption had a 3.5 to 4.5-fold increased risk of viral non-suppression, depending on the model (aOR ranging from 2.49 to 4.55). This increased risk persisted after resuming treatment and adds to the documented adverse consequences of interruptions: slower immune reconstitution, faster progression to AIDS, and increased mortality.
This finding is particularly concerning as the cumulative risk of interruption, already at 38.2% in this cohort, is expected to increase with treatment duration. The authors suggest that these interruptions could further compromise ART programs in the context of recent cuts in international funding.
The analysis also indicated that the risk of non-suppression decreased with age, duration on treatment, and a higher initial CD4 count. Women participants showed a lower risk of non-suppression (aOR of 0.76 to 0.83) compared to men.
Study Strengths and Limitations
The authors highlight three major strengths of their study: the exceptional cohort size, the prolonged follow-up duration (median of 4.9 years, data from 2005 to 2023), and the use of advanced statistical methods to estimate the causal effect of dolutegravir from real-world follow-up data.
Limitations include a high proportion of missing viral load measurements (41% of theoretical measurement dates), requiring imputation, and the lack of data on treatment adherence and socioeconomic status.
This study provides robust evidence supporting the continued deployment of dolutegravir-based regimens. It also underscores the urgent require to develop interventions to prevent treatment interruptions and support return to care, crucial challenges for the sustainability of ART programs in a context of uncertain funding.
Reference
Moolla H, Kassanjee R, Euvrard J, Maartens G, Prozesky HW, Fox MP et al. Estimates and predictors of HIV viral non-suppression in South African adults on antiretroviral treatment. Journal of the International AIDS Society, 2026;29:e70076. DOI: 10.1002/jia2.70076
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