title: Delay in sexual maturation in perinatally HIV-infected youths is mediated by poor growth.
abstract: To evaluate the association between HIV infection and sexual maturation, and mediation of this association by HIV effects on growth.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: aDepartment 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bellavia
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: Linda A
authors.initials: LA
authors.lastname: DiMeglio
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Abzug
authors.forename: Kunjal
authors.initials: K
authors.lastname: Patel
authors.forename: Denise L
authors.initials: DL
authors.lastname: Jacobson
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Geffner
mesh_terms: D000293:Adolescent; D002648:Child; D002657:Child Development; D005260:Female; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012741:Sexual Maturation; D055815:Young Adult