Earlier Antiretroviral Therapy Initiation and Decreasing Mortality among HIV-infected Infants Initiating Antiretroviral Therapy within 3 Months of Age in South Africa, 2006-2017

Background: Early infant diagnosis of HIV and antiretroviral therapy (ART) has been rapidly scaled-up. We aimed to examine the effect of expanded access to early ART on the characteristics and outcomes of infants initiating ART. Methods: From 9 cohorts within the International epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, we included infants with HIV initiating ART ≤3 months of age between 2006 and 2017. We described ART initiation characteristics and the probability of mortality, loss to follow-up (LTFU) and transfer out after 6 months on ART and assessed factors associated with mortality and LTFU. Results: A total of 1847 infants started ART at a median age of 60 days [interquartile range: 29-77] and CD4 percentage (%) of 27% (18%-38%). Across ART initiation calendar periods 2006-2009 to 2013-2017, ART initiation age decreased from 68 (53-81) to 45 days (7-71) (P < 0.001), median CD4% improved from 22% (15%-34%) to 32% (22-43) (P < 0.001) and the proportion with World Health Organization clinical disease stage 3 or 4 declined from 81.6% to 32.7% (P < 0.001). Overall, the 6-month mortality probability was 5.0% and LTFU was 20.4%. Mortality was 10.6% (95% confidence interval: 7.8%-14.4%) in 2006-2009 and 4.6% (3.1%-6.7%) in 2013-2017 (P < 0.001), with similar LTFU across calendar periods (P = 0.274). Pretreatment weight-for-age Z score <-2 was associated with higher mortality. Conclusions: Infants with HIV are starting ART younger and healthier with associated declines in mortality. However, the risk of mortality remained undesirably high in recent years. Focused interventions are needed to optimize the benefits of earlier diagnosis and treatment.