The Effect of Early Initiation of Antiretroviral Treatment in Infants on Pediatric AIDS Mortality in South Africa A Model-based Analysis

Background: Guidelines for treatment of pediatric HIV have recently changed to recommend that all infants who are identified as HIV-infected should start antiretroviral treatment (ART) immediately, regardless of their immunologic or clinical status. This study aims to assess the likely impact of this change in guideline in South Africa. Methods: A mathematical model was developed to simulate mother-to-child transmission of HIV, disease progression, and death of HIV-infected children <15 years of age. The model is calibrated to South African data sources, including prevention of mother-to-child transmission program coverage data, pre-ART survival data, ART program statistics, and pediatric HIV prevalence studies. Results: Relative to what would be expected in the absence of early ART initiation, the number of infant AIDS deaths over the 2010-2025 period is expected to drop by 23.6% (95% confidence interval [CI]: 22.5-24.5%) at current levels of polymerase chain reaction (PCR) diagnosis, and by 34.2% (95% CI: 32.7-35.6%) if PCR diagnosis increases to 80% of perinatally infected infants at 2 months. However, the pediatric HIV disease burden has shifted toward older children in recent years. The effect of early ART on total pediatric AIDS mortality during the 2010-2025 period is therefore modest: a 9.8% reduction (95% CI: 7.9-12.6%) at current levels of PCR diagnosis, and a 14.2% reduction (95% CI: 11.4-18.2%) if PCR coverage increases to 80% of perinatally infected infants. Conclusion: The changes in ART guidelines for infants will have a significant impact on pediatric AIDS mortality at young ages, but further efforts are required to reduce the substantial growing AIDS mortality in older children.