TOPLINE:

High maternal HIV viral load during pregnancy was associated with earlier pubertal onset by age 9 in boys who were exposed to HIV in utero but remained uninfected. These boys were also more likely than unexposed, uninfected boys to have reached puberty by age 9; however, the difference was not statistically significant.

METHODOLOGY:

• Researchers analyzed 215 HIV-exposed but uninfected children (107 boys) to evaluate the association between gestational exposure to HIV and puberty onset comparing them with 344 healthy, HIV-unexposed, uninfected children (162 boys).
• Puberty onset by the age of 9 years was assessed using Tanner staging, defined as stage ≥ 2 for sex-specific puberty indicators — breast development and pubic hair in girls and genitalia and pubic hair in boys.
• The study also assessed whether the use of maternal protease inhibitors, CD4 count, and high viral load (≥ 400 HIV copies per mL) were linked to puberty onset in 227 HIV-exposed but uninfected children.

TAKEAWAY:

• HIV-exposed but uninfected children showed higher rates of puberty onset across all indicators than HIV-unexposed, uninfected children (35.2% vs 23.1% for breasts and 32.4% vs 14.8% for pubic hair in girls; 15.0% vs 9.9% for genitalia and 11.2% vs 3.7% for pubic hair in boys).
• High maternal viral load during pregnancy was associated with an increased likelihood of puberty onset in boys who were HIV-exposed but uninfected for both indicators (adjusted relative risk [aRR], 12.6 for genitalia; aRR, 9.85 for pubic hair); however, these estimates had wide CI levels.
• A nonsignificant trend toward early puberty onset was observed among boys who were HIV-exposed but uninfected than boys who were HIV-unexposed and uninfected (aRR, 2.07; P = .09 for genitalia; aRR, 3.55; P = .07 for pubic hair).
• In boys, gestational protease inhibitor exposure showed a nonsignificant trend toward a lower likelihood of puberty onset, and maternal CD4 count showed no association; in girls, puberty onset did not differ by gestational HIV exposure or other assessed factors.

IN PRACTICE:

“The greater impact on pubertal onset in male CHEU [children HIV-exposed but uninfected] may be due, in part, to inherent sex-dependent differences in the intrauterine environment, with the placenta being less protective to inflammatory and infectious agents for the male fetus, and to coping strategies in the face of adversity, with the male fetus being less adaptable to gestational changes,” the authors wrote.

SOURCE:

This study was led by Lena Serghides, PhD, University of Toronto, Toronto, Ontario, Canada. It was published online on November 19, 2025, in JAIDS Journal of Acquired Immune Deficiency Syndrome.

LIMITATIONS:

This study did not collect data on the puberty trajectory beyond the age of 9 years or include hormonal assessments. The HIV-unexposed uninfected children belonged to a different cohort and differed notably in racial distribution and BMI from those who were HIV-exposed but uninfected. Finally, evaluation of gestational exposure to antiretrovirals was constrained by limited number of children taking newer antiretrovirals.

DISCLOSURES:

This study was part of the Pediatric HIV/AIDS Cohort Study network, which was supported by multiple sources, including the Eunice Kennedy ShriverNational Institute of Child Health and Human Development; Office of the Director, National Institutes of Health; and National Institute of Dental and Craniofacial Research. One author disclosed receiving support from a Canada Research Chair in Maternal-Child Health and HIV.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.