Delay in sexual maturation in perinatally HIV-infected youths is mediated by poor growth

Abstract

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 IMPAACT P219/219C Study (1993–2007) and the PHACS Adolescent Master Protocol (2007–2015), including perinatally HIV-infected (PHIV) and HIV-exposed uninfected (PHEU) youth. 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 body mass index (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 youth matured approximately 6 months later on average than PHEU (n=221 girls, 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 youth attain sexual maturity later on average than PHEU youth. Much of this difference may be attributable to deficient growth, suggesting directions for future interventions.

Stunting and growth velocity of adolescents with perinatally acquired HIV: differential evolution for males and females. A multiregional analysis from the IeDEA global paediatric collaboration

“…The growth differences observed between males and females in this study were not fully explained by the available data. The pubertal development of APH could be different for males and females and have varying effects on growth, but the literature on this topic is scarce , especially in LMICs . In the US, compared to HIV‐exposed but uninfected adolescents, APH had delayed pubertal onset, from six to eight months later in females and 10 to 11 months later in males.…”

“…Adolescence is the second most important period of growth after the first year of life , hence these factors may hinder pubertal growth spurt for APH. Chronic diseases, malnutrition and HIV infection during childhood could also delayed puberty, worsening growth retardation during adolescence for APH .…”

Older age at initiation of antiretroviral therapy predicts low bone mineral density in children with perinatally-infected HIV in Zimbabwe

“…Our findings show that stunting is not a proxy for low size-adjusted bone density. Adolescent skeletal growth is not linearly and structurally uniform; peak height velocity precedes peak bone content accrual [29], yet how bone is accrued in the context of HIV infection with associated delayed puberty, and hence skeletal maturation [30], is poorly understood. Despite CWH being on average 2.7 years older than those uninfected, only 14% more CWH had entered puberty.…”

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

“…We also observed an association between stunting and later growth spurts, but only in girls. The potential role of anthropometric parameters in early childhood on growth during puberty was highlighted in a study of 2539 young people with vertically acquired HIV and HIV-exposed uninfected (HEU) young people from the USA [6]. Young people living with HIV reached sexual maturity on average 6 months later than the HEU group, but differences in HAZ prior to puberty accounted for up to 98% of the delay in boys and (together with zBMI) 74% in girls, suggesting much of the delay may be attributable to earlier poor growth [6].…”

“…Delays in pubertal development have been reported in young people with HIV [3–7], with the onset of puberty [5] and sexual maturation [6] occurring 6 months later compared with HIV-exposed uninfected young people (HEU). Earlier puberty in the general population is associated with being taller and having higher BMI throughout childhood [8], and poor growth in children with HIV has been shown to account for much of the delay in reaching sexual maturity [6]. There is also evidence that children starting ART with low height-for-age z -scores experience delays in the onset of puberty independently of age at ART initiation [3].…”