Infant HIV-protection: Comparing antiretroviral therapy, maternal and infant factors influence on infant HIV acquisition in Uganda: A six-year real-world experience

Although antiretroviral therapy (ART) scale up has markedly lowered vertical transmission, the relative contribution of ART regimens, maternal factors, and infant practices within Prevention of vertical transmission (PVT) programs is not fully understood. We assessed the comparative influence of maternal and infant factors on infant HIV positivity. We retrospectively reviewed records of 962 HIV exposed infants attending the Mildmay Uganda PVT clinic between 2018 and 2023. Of these, 918 were mother-infant pairs. Descriptive statistics summarised maternal and infant characteristics. Associations were assessed using Chi square or Fisher exact tests. Two independent logistic regression models identified infant and maternal factors associated with HIV positivity. Pseudo R² evaluated model performance and area under the curve measured discrimination. Among 918 mother-infant pairs, HIV positivity was 1.96% (18). PI based regimens were associated with increased odds of HIV positivity (aOR 22.89, 95% CI 2.20-238.14, p = 0.009). Among maternal factors, HIV positivity differed significantly by age group (p < 0.001) and viral load suppression status (p = 0.025), with viral load non-suppression independently increasing risk (aOR 4.97, 95% CI 1.45-17.10, p = 0.011). Among infant factors, mixed feeding (aOR 26.87, 95% CI 5.82-124.10) and no breastfeeding (aOR 86.94, 95%CI 17.40-434.56) were strongly associated with HIV positivity (both p < 0.001). The maternal model showed modest explanatory capacity (pseudo R² 0.09) and acceptable discrimination (AUC 0.74; bootstrap AUC 0.70, 95% CI 0.58-0.83). The infant model demonstrated stronger performance (pseudo R² 0.51) with excellent discrimination (AUC 0.94; cross-validated AUC 0.95, 95% CI 0.79-0.95).While maternal ART regimen and viral suppression are critical, infant feeding practices appear to have a stronger influence on infant HIV positivity. Strengthening counselling on optimal infant feeding practices and timely HIV prophylaxis is essential to achieve elimination of paediatric HIV.