Longitudinal study on insulin resistance and metabolic syndrome in children with perinatal HIV infection and HIV exposed uninfected children in South Africa

BACKGROUND: HIV is associated with insulin resistance and Metabolic Syndrome, driven by HIV-associated immune dysregulation and by antiretroviral therapy (ART). However, few longitudinal studies have been conducted in children living with perinatally-acquired HIV (CLpHIV). We evaluated the trajectory of insulin resistance and Metabolic Syndrome in CLpHIV compared to children who are HIV-unexposed and uninfected (CHUU), and children who are HIV-exposed and uninfected (CHEU).
METHODS: The study included children previously part of the Children with HIV Early antiRetroviral (CHER) trial and P1060 trial followed at Tygerberg Children's Hospital in South Africa between 2014 and 2020, along with CHEU and CHUU from the same communities. The cohort comprised 485 children, with 141 CLpHIV, 169 CHEU and 175 CHUU, with a median age at baseline of 9 years. The main outcome was the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and secondary outcomes included LDL cholesterol, triglyceride-to-HDL ratio, android fat mass and systolic blood pressure. We used a mixed effects model to model the progression of metabolic indicators over time in each HIV group. Directed Acyclic Graph analysis was used to identify covariates, whereafter the following were considered as confounders: gender, height, age group, Tanner puberty stage and ethnicity.
RESULTS: Adjusted mean HOMA-IR was 15% (95%CI:2%'29%) greater in CLpHIV than CHUU. Adjusted mean triglyceride-to-HDL ratio was 48%(95%CI:35%'62%) greater in CLpHIV than CHUU, and the adjusted mean LDL was 0.25 mmol/L greater in CLpHIV than CHUU (95%CI:0.11'0.40). In all analyses, no significant difference was found between CHEU and CHUU.

Figure 1: Predicted values for each metabolic indicator over time, by HIV group

CONCLUSIONS: CLpHIV have persistently elevated insulin resistance, triglyceride-to-HDL ratio and LDL cholesterol into puberty, and therefore should be monitored carefully for subclinical cardiovascular disease and receive appropriate preventative interventions, as CLpHIV will have a lifelong exposure to HIV-associated immune dysregulation and ART.