Growth, infection, and humoral immunity in children who are HIV exposed and uninfected

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Background Children who are HIV-exposed uninfected (HEU) show greater morbidity and mortality than HIV-unexposed children (HUU). In this study we investigate sex differences in growth, infection rates and antibody response among HEU and HUU infants. Methods The study enrolled 107 pregnant women with HIV and 103 pregnant women without HIV with follow-up of their infants from birth to 12 months of age. Study measures assessed included growth parameters, the prevalence of children with overt disease symptoms as reported by the mother, PCR-based assessment of infections (cytomegalovirus (CMV), respiratory syncytial virus (RSV), rhinovirus, influenza A & B, rotavirus and malaria) as well as antibody profile to CMV, RSV and enterovirus infections. Results Compared to male HUU, male HEU infants had higher stunting at month 3 (0% vs 17.4%; P = 0.01) and month 12 (12.5% vs 38.9%; P = 0.03). Additionally, they showed transiently lower Weight-for-age-z-scores at 3 months (1.07 vs 0.05, P = 0.04), with higher risk of rhinorrhea (RR = 2.29, P = 0.02) and lower enterovirus titers at birth (P = 0.0066). Female HEU showed transiently higher stunting at 6 months (0% vs 21%; P = 0.01) and lower CMV viremia at 6 months, with elevated CMV antibody titers at 3 months (P = 0.04) compared to female HUU. With prevalence ranging from 25%–61%, CMV and Rhinovirus infections were dominant in all groups. HEU and HUU exhibited similar antibody decay and acquisition patterns for CMV, RSV, and Enterovirus. Conclusion Overall, HEU and HUU infants showed similar growth, infection and humoral immune profiles. However, exploratory analyses identified transient sex-specific differences, with male HEU infants displaying poorer growth trajectories and selected infection-related vulnerabilities, highlighting the need for larger studies to clarify sex-dependent effects of in utero exposure to HIV/ART.

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