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

We assessed whether children/adolescents ages 9-11 years with in-utero HIV exposure but uninfected (CAHEU) had a 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.

An observational cross-sectional study.

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 girls, and male genitalia in boys) among adolescents aged 9-11 years 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.

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% confidence interval: 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 vs. zidovudine were observed.

In this small Botswana cohort, we observed no consistent differences in pubertal onset by in-utero HIV exposure status or by in-utero antiretroviral exposure. Longitudinal studies are needed to confirm these findings.