Antiretroviral therapy (ART) is associated with dyslipidemia and cardiovascular disease in adults infected with HIV. For children perinatally infected with HIV, ART exposure is lifelong and early-onset dyslipidemia could have significant long-term effects. We examined cholesterol levels in children during the first year after exposure to a new ART regimen (initiation or switch). In 52 children, total cholesterol increased by 30.5 and 43 mg/dL at 6 and 12 months, respectively (P < 0.001). Low-density lipoprotein cholesterol made the largest contribution, but high-density lipoprotein cholesterol also increased within months of therapy alteration. Early identification of these children and intervention could mediate potential increased risk for future cardiovascular disease.