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Pubertal onset in children with perinatal HIV infection in the era of combination antiretroviral treatment

Williams, Paige L.a,b; Abzug, Mark J.c; Jacobson, Denise L.a; Wang, Jiajiaa; Van Dyke, Russell B.d; Hazra, Rohane; Patel, Kunjala,f; Dimeglio, Linda A.g; Mcfarland, Elizabeth J.h; Silio, Margaritad; Borkowsky, Williami; Seage, George R. IIIa,f; Oleske, James M.j; Geffner, Mitchell E.kfor the International Maternal Pediatric and Adolescent AIDS Clinical Trials P219219C Study and the Pediatric HIVAIDS Cohort Study

doi: 10.1097/QAD.0b013e328361195b
Epidemiology and Social

Objective: To evaluate associations of perinatal HIV infection, HIV disease severity, and combination antiretroviral treatment with age at pubertal onset.

Design: 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.

Conclusion: 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.

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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.

Correspondence to Dr Paige Williams, Center for Biostatistics in AIDS Research, Harvard School of Public Health, 655 Huntington Ave, FXB-607, Boston, MA 02115-6017, USA. Tel: +1 617 432 3872; fax: +1 617 432 2832; e-mail:

Received 7 January, 2013

Revised 21 February, 2013

Accepted 10 March, 2013

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© 2013 Lippincott Williams & Wilkins, Inc.