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Delay in sexual maturation in perinatally HIV-infected youths is mediated by poor growth
Andrea Bellavia1, Paige L Williams, Linda A DiMeglio
1aDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts bSection of Pediatric Endocrinology and Diabetology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana cEunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland dDepartment of Pediatrics (Infectious Diseases), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado eDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts fTulane University School of Medicine, New Orleans, Louisiana gSaban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
Insights
Perinatally HIV-infected (PHIV) youths experience delayed sexual maturation compared to HIV-exposed uninfected (PHEU) youths. Growth deficiencies, particularly in height and BMI, significantly mediate this delay in PHIV adolescents.
Area of Science:
- Pediatric Endocrinology
- Infectious Diseases
- Adolescent Health
Background:
- Human Immunodeficiency Virus (HIV) infection can impact various aspects of child development.
- Understanding the effects of HIV on sexual maturation is crucial for adolescent health management.
Purpose of the Study:
- To investigate the association between perinatally HIV-infected (PHIV) status and the timing of sexual maturation.
- To determine if HIV-related growth deficits mediate the relationship between HIV infection and delayed sexual maturation in adolescents.
Main Methods:
- Analysis of pooled data from two large longitudinal cohort studies (International Maternal Pediatric Adolescent AIDS Clinical Trials and Pediatric HIV/AIDS Cohort Study).
- Evaluation of age at sexual maturity using physician-assessed pubertal staging in 2539 PHIV and HIV-exposed uninfected (PHEU) adolescents.
- Application of interval-censored regression and mediation analyses incorporating height and BMI Z-scores.
Main Results:
- PHIV youths demonstrated delayed sexual maturation by approximately 6 months on average compared to PHEU youths.
- In girls, BMI and height Z-scores mediated up to 74% of the association between HIV infection and later maturation.
- In boys, height Z-scores mediated up to 98% of the HIV effect on age at sexual maturity.
Conclusions:
- Perinatally HIV-infected adolescents achieve sexual maturity later than their HIV-exposed uninfected peers.
- Growth deficiencies play a significant role in mediating the delayed sexual maturation observed in PHIV youths, highlighting potential targets for intervention.
Objective:
To evaluate the association between HIV infection and sexual maturation, and mediation of this association by HIV effects on growth.
Design:
Pooled data were analyzed from two longitudinal cohort studies, the International Maternal Pediatric Adolescent AIDS Clinical Trials P219/219C Study (1993-2007) and the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (2007-2015), including perinatally HIV-infected (PHIV) and HIV-exposed uninfected (PHEU) youths.
Methods:
We evaluated age at sexual maturity among 2539 PHIV and PHEU adolescents based on annual physician-assessed pubertal staging measures. Interval-censored regression models were used to evaluate associations of HIV infection with age at maturity. Mediation analyses accounting for height and BMI Z-scores at specific ages were used to estimate direct and indirect effects of HIV infection on age at sexual maturity.
Results:
Mean ages at sexual maturity for PHIV girls (n = 1032) were 15.5 years for both female breast and pubic hair and 15.9 and 15.8 years for PHIV boys (n = 1054) for genitalia and pubic hair, respectively. PHIV youths matured approximately 6 months later on average than PHEU (n = 221 girls and 232 boys), and this difference persisted after adjustment for race/ethnicity and birth cohort. BMI and height Z-scores mediated the association between HIV infection and later maturation in girls, accounting for up to 74% of the total HIV effect. Only height Z-scores mediated the effect of HIV on male age at maturity, accounting for up to 98% of the HIV effect.
Conclusion:
PHIV youths attain sexual maturity later on average than PHEU youths. Much of this difference may be attributable to deficient growth, suggesting directions for future interventions.