Among perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth, we evaluated the contributions of home environment, psychosocial, and demographic factors and, among PHIV only, HIV disease severity and antiretroviral treatment (ART), to cognitive functioning (CF) and behavioral functioning (BF). A structural equation modeling (SEM) approach was utilized. Exploratory factor analysis was used to reduce predictor variables to major latent factors. SEMs were developed to measure associations between the latent factors and CF and BF outcomes. Participants included 231 PHIV and 151 PHEU youth (mean age = 10.9 years) enrolled in the PHACS adolescent master protocol. Youth and caregivers completed assessments of CF, BF, psychosocial factors and HIV health. Medical data were also collected. Clusters of predictors were identified, establishing four parsimonious SEMs: child-assessed and caregiver-assessed BF in PHIV and PHEU youth. Among both groups, higher caregiver-child stress predicted worse BF. Caregiver resources and two disease severity variables, late presenter and better past HIV health, were significant predictors of CF in PHIV youth. Higher youth CF was associated with better caregiver-reported BF in both groups. Caregiver resources predicted caregiver-reported BF in PHEU youth, which was mediated via youth CF. Among PHIV youth, better past HIV health and caregiver resources mediated the effects of CF on caregiver-assessed BF. Using SEMs, we found a deleterious impact of caregiver and child stress on BF in both groups and of HIV disease factors on the CF of PHIV youth, reinforcing the importance of early comprehensive intervention to reduce risks for impairment.

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