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To investigate the prevalence of and risk factors for insulin resistance (IR) in a cohort of youth living with perinatally acquired HIV (YLPHIV) receiving antiretroviral treatment (ART). A cross-sectional analysis of IR in YLPHIV and age-matched HIV-uninfected youth enrolled in the Cape Town Adolescent Antiretroviral Cohort. South African youth ages 9-14 years, with perinatally acquired HIV who were on ART for &gt;6 months and age-matched HIV-uninfected adolescents, were eligible. The homeostatic model assessment of insulin resistance (HOMA-IR), calculated from fasting insulin and glucose measurements at enrollment, was used to assess IR. Multiple linear regression was used to examine adjusted associations between HOMA and HIV-related and traditional cardiovascular risk factors. Of 448 adolescents, 385 (85.9%) were YLPHIV; median age was 12.1 years [interquartile range (IQR): 10.8-13.5], and 50.4% were female. Median duration on ART was 7.5 (IQR: 4.5-9.2) years. The prevalence of IR in YLPHIV was 18%. Among YLPHIV, waist circumference (ß = 0.01, p = .01), hypertriglyceridemia (ß = 0.07, p = .01), CD4 count &gt;500 cells/mm 3 (ß = 0.08, p = .02), or prior use of abacavir (ß = 0.06, p = .04) were associated with increased HOMA, after adjusting for age, sex, body mass index, and Tanner stage. In a South African cohort of YLPHIV on ART, IR was not significantly different from uninfected adolescents. YLPHIV with traditional cardiovascular risk factors or abacavir exposure may be at higher risk for IR.

Insulin Resistance in South African Youth Living with Perinatally Acquired HIV Receiving Antiretroviral Therapy