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Combination antiretroviral therapy has allowed youth with perinatal HIV infection (PHIV+) to live into adulthood, but many youth may experience metabolic and body composition changes that predispose to greater cardiovascular disease (CVD) risk. This longitudinal study evaluated changes in body composition measured by dual-energy radiograph absorptiometry (DXA) in a cohort of PHIV+ youth compared with HIV− controls over a 7-year period.PHIV+ youth and HIV− controls were prospectively enrolled in a single-site study to assess nutrition and CVD risk. Anthropometrics and DXA scans were longitudinally obtained to assess percent body fat and regional fat distribution. Using general linear models, we analyzed differences in body composition and anthropometric measures by sex between PHIV+ youth and controls over time.Two hundred thirty-five participants (156 PHIV+ and 79 HIV− controls) with at least 1 DXA performed since study enrollment were included for analysis. During the study period, 471 DXAs were obtained in the PHIV+ group and 95 in HIV− controls. PHIV+ females demonstrated greater increase in weight and body mass index over time compared with HIV− females, and significant increases in total percent body fat [estimate = 1.212 (95% confidence interval: 0.837–1.587) percent per year; P < 0.001) and percent trunk fat [1.3818 (95% confidence interval: 0.922–1.84); P < 0.001] compared with HIV− females and PHIV+ males.PHIV+ females demonstrate an unfavorable change in fat redistribution and percent body fat over time that exceeds the pattern seen in PHIV+ males or HIV− females. Providers should have heightened awareness of body composition changes of PHIV+ females that may eventually lead to increased CVD risk.