Increased infectious-cause hospitalization among infants who are HIV-exposed uninfected compared to HIV-unexposed.

OBJECTIVES: Increased risk of morbidity and hospitalization has been observed in children who are HIV-exposed uninfected (HEU) compared to HIV-unexposed uninfected (HUU). Studies in the era of universal maternal antiretroviral treatment (ART) are limited. DESIGN: Prospective cohort. METHODS: We investigated hospitalization between 29 days and 12 months of life in a South African cohort of infants born February 2017 - January 2019 (HEU=455; HUU=458). All mothers known with HIV during pregnancy received ART. We reviewed hospital records and classified and graded infectious diagnoses using a standardized tool. We examined factors associated with infectious-cause hospitalization using mixed-effects Poisson regression. RESULTS: Infants HEU vs. HUU had higher all-cause and infectious-cause hospitalization (13% vs. 7%, p = 0.004 and 10% vs. 6%, p = 0.014 respectively). Infectious causes accounted for most hospitalizations (77%). More infants HEU were hospitalized with severe or very severe infections than those HUU (4% vs. 3% severe; 6% vs. 3% very severe; p = 0.041). Mortality (<1%) did not differ between groups. HIV exposure was a significant risk factor for infectious-cause hospitalization (aIRR = 2.8; 95% CI 1.5-5.4). Although increased incidence of preterm birth (14% vs. 10%; p < 0.05) and shorter duration of breastfeeding (44% vs. 68% breastfed for ≥3 months, p < 0.001) among infants HEU vs. HUU contributed to increased hospitalization, they did not account for all the increased risk. CONCLUSION: Infectious-cause hospitalization incidence was higher among infants HEU vs. HUU, likely partly due to higher incidence of preterm birth and lower breastfeeding rates among infants HEU. The increased infectious disease burden in HEU infants has important implications for health services in sub-Saharan Africa.