Longitudinal comparison of insulin resistance and dyslipidemia in children with and without perinatal HIV infection in South Africa

Abstract

Introduction: HIV infection is associated with insulin resistance and dyslipidaemia driven by HIV-associated immune dysregulation and antiretroviral therapy (ART). Children living with perinatally acquired HIV (CHIV) face many decades of exposure to these factors. We evaluated the longitudinal trajectory of insulin resistance and dyslipidaemia in CHIV and HIV-exposed uninfected children (CHEU), compared with children HIV-unexposed (CHU). Methods: Four hundred and eighty-five children (141 CHIV, 169 CHEU, 175 CHU) aged 5–16 years, previously part of CHER and P1060 trials, were followed annually at Tygerberg Children's Hospital, South Africa. The primary outcome was Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Secondary outcomes included low-density lipoprotein (LDL) cholesterol, triglyceride-to-HDL ratio, android fat mass and SBP. Outcomes were evaluated using linear mixed effects models, adjusting for potential confounders. Results: CHIV had 73% greater HOMA-IR than CHU in ages 6–8 years (95% CI 15.9–158.2%, P < 0.001), and 24.7% greater HOMA-IR than CHU in ages 9–10 years (0.3–55.1%, P = 0.04). By 10–11 years, the difference was not significant (P = 0.161). Longitudinally, triglyceride-to-HDL was 47.94% (34.50–62.73%, P < 0.001) higher in CHIV vs. CHU; LDL was 0.25 mmol/l (0.10–0.39, P = 0.001) higher in CHIV vs. CHU; android fat mass was 11.57% (−21.11 to −0.87%, P = 0.035) lower in CHIV than CHU. No significant difference in SBP was found. CHEU and CHU had similar outcomes. Conclusion: Early-treated CHIV have elevated insulin resistance, which resolves with time. Triglyceride-to-HDL ratio and LDL cholesterol were elevated into puberty. CHIV should be monitored for insulin resistance, dyslipidaemia and subclinical cardiovascular disease.