Pubertal onset in children with in utero HIV/antiretroviral exposure in Botswana

Objective: We assessed whether children/adolescents ages 9–11 with in utero HIV exposure but uninfected (CAHEU) had lower chance of pubertal onset compared to children/adolescents who were HIV-unexposed (CAHU) during gestation. Among CAHEU, we assessed the association of in utero combination antiretroviral therapy (ART) vs. zidovudine monotherapy exposure with pubertal onset. Design: Observational cross-sectional study. Methods: Pubertal onset (Tanner stage ≥2) was classified by sex and by in utero HIV exposure status for each puberty indicator (pubic hair, breast development in females, and male genitalia in males) among adolescents aged 9–11 from the Botswana-based FLOURISH study. Logistic regression models were fit to assess the association of in utero HIV/ARV exposure with pubertal onset, adjusting for age at assessment and potential confounders. Among CAHEU, we compared the occurrence of pubertal onset for ART-exposed vs zidovudine-exposed. Results: We evaluated 325 children/adolescents (228 CAHEU) at median age (IQR) 10.0 years (9.5, 10.6 years). CAHEU had lower mean BMI Z-scores at Tanner assessment (-0.36 vs 0.19) than CAHU. While female CAHEU had higher odds of pubertal onset by pubic hair compared with female CAHU (adjusted odds ratio=2.75, 95% CI: 1.04, 7.30), no other differences in pubertal onset were observed by in utero HIV exposure. Among CAHEU, no differences in pubertal onset by in utero exposure to ART versus zidovudine were observed. Conclusion: In this small Botswana cohort, we observed no consistent differences in pubertal onset by in utero HIV exposure status or by in utero ARV exposure. Longitudinal studies are needed to confirm these findings.