Association of hypercholesterolemia incidence with antiretroviral treatment, including protease inhibitors, among perinatally HIV-infected children

CONTEXT: Antiretroviral therapy has been associated with hypercholesterolemia in HIV-infected children. Few longitudinal studies have been conducted to examine this association, however. OBJECTIVE: To evaluate the incidence of and risk factors for development of hypercholesterolemia in a large pediatric study. DESIGN: Prospective cohort study (Pediatric AIDS Clinical Trials Group 219C). PARTICIPANTS: A total of 2122 perinatally HIV-infected children free of hypercholesterolemia at entry. OUTCOME: Development of hypercholesterolemia (total cholesterol ≥220 mg/dL at 2 consecutive visits). Cox proportional hazards models were used to evaluate risk factors. RESULTS: Thirteen percent of children had hypercholesterolemia at entry, and an additional 13% developed hypercholesterolemia during follow-up for an incidence rate of 3.4 cases per 100 person-years (95% confidence interval [CI]: 3.0 to 3.9). After adjustment for age, boosted protease inhibitor (PI) use (hazard ratio [HR] = 13.9, 95% CI: 6.73 to 28.6), nonboosted PI use (HR = 8.65, 95% CI: 4.19 to 17.9), and nonnucleoside reverse transcriptase inhibitor use (HR = 1.33, 95% CI: 1.04 to 1.71) were associated with increased risk of hypercholesterolemia, and higher viral load was protective (>50,000 vs. ≤400 copies/mL; HR = 0.59, 95% CI: 0.39 to 0.90). Self-reported adherent subjects had higher risk. CONCLUSIONS: PIs were significant risk factors for hypercholesterolemia. Higher viral load was protective and may reflect nonadherence. Further follow-up is critical to evaluate long-term consequences of chronic PI exposure and hypercholesterolemia.