title: Pubertal onset in children with perinatal HIV infection in the era of combination antiretroviral treatment.
abstract: OBJECTIVE
  To evaluate associations of perinatal HIV infection, HIV disease severity, and combination antiretroviral treatment with age at pubertal onset.
  
  
  METHODS
  Analysis of data from two US longitudinal cohort studies (IMPAACT 219C and PHACS AMP), conducted during 2000-2012, including perinatally HIV-infected (PHIV) and HIV-exposed but uninfected (HEU) youth. Tanner stage assessments of pubertal status (breast and pubic hair in girls; genitalia and pubic hair in boys) were conducted annually.
  
  
  METHODS
  We compared the timing of pubertal onset (Tanner stage ≥2) between PHIV and HEU youth using interval-censored models. For PHIV youth, we evaluated associations of HIV disease severity and combination antiretroviral treatment with age at pubertal onset, adjusting for race/ethnicity and birth cohort.
  
  
  RESULTS
  The mean age at pubertal onset was significantly later for the 2086 PHIV youth compared to the 453 HEU children (10.3 vs. 9.6, 10.5 vs. 10.0, 11.3 vs. 10.4, and 11.5 vs. 10.7 years according to female breast, female pubic hair, male genitalia, and male pubic hair staging, respectively, all P < 0.001). PHIV youth with HIV-1 RNA viral load above 10, 000 copies/ml (vs. ≤10, 000 copies/ml) or CD4% below 15% (vs. ≥15%) had significantly later pubertal onset (by 4-13 months). Each additional year of combination antiretroviral treatment was associated with a 0.6-1.2-month earlier mean age at pubertal onset, but this trend did not persist after adjustment for birth cohort.
  
  
  CONCLUSIONS
  Pubertal onset occurs significantly later in PHIV than in HEU youth, especially among those with more severe HIV disease. However, in the current era, combination antiretroviral treatment may result in more normal timing of pubertal onset.
authors.affiliation: aCenter for Biostatistics in AIDS Research bDepartment of Biostatistics, Harvard School of Public Health, Boston, Massachusetts cDepartment of Pediatrics (Infectious Diseases), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado dTulane University School of Medicine, New Orleans, Louisiana eEunice Kennedy Shriver National Institute of Child Health & Human Development, Bethesda, Maryland fDepartment of Epidemiology, Harvard School of Public Health, Boston, Massachusetts gSection of Pediatric Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana hDepartment of Pediatrics, University of Colorado School of Medicine, Denver, Colorado iNew York University School of Medicine, New York jDepartment of Pediatrics, New Jersey Medical School, Newark, New Jersey kSaban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Abzug
authors.forename: Denise L
authors.initials: DL
authors.lastname: Jacobson
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Kunjal
authors.initials: K
authors.lastname: Patel
authors.forename: Linda A
authors.initials: LA
authors.lastname: Dimeglio
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: McFarland
authors.forename: Margarita
authors.initials: M
authors.lastname: Silio
authors.forename: William
authors.initials: W
authors.lastname: Borkowsky
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.forename: James M
authors.initials: JM
authors.lastname: Oleske
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Geffner
mesh_terms: D000293:Adolescent; D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D005260:Female; D006678:HIV / Q000302:isolation & purification*; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011628:Puberty, Delayed; D012367:RNA, Viral / Q000097:blood; D014481:United States; D019562:Viral Load; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral