Metabolic syndrome and its risk factors among adults living with HIV receiving antiretroviral therapy in Zambia: an ambidirectional cohort study

Effective antiretroviral therapy (ART) has significantly improved the survival of people living with HIV (PWH) while concurrently ushering in a new challenge of cardiometabolic complications. Despite advancements in treatment, there is a paucity of epidemiological and longitudinal data on metabolic changes among PWH receiving ART in sub-Saharan Africa, particularly with the adoption of integrase strand transfer inhibitors (INSTIs). This study estimated the incidence of metabolic syndrome (MetS) and identified associated risk factors among adult PWH at a tertiary health facility in Zambia. We enrolled PWH initiating care (n = 12) and those on ART for ≥6 months (n = 313), without prevalent MetS, at Livingstone University Teaching Hospital between April 2019 and April 2020. Participants returned for a follow-up visit between December 2022 and June 2023. Demographic, clinical and laboratory data were collected by structured questionnaire and medical chart abstraction. The primary outcome was the incidence of MetS, defined as having three or more of the following criteria: elevated waist circumference (WC, ≥ 94 cm for men, ≥ 80 cm for women), elevated fasting blood glucose (FBG, ≥ 5.6 mmol/L), low level of high-density lipoprotein cholesterol (HDL-c, < 1.0 mmol/L for men, < 1.3 for women), elevated blood pressure (BP) (systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg), and elevated triglycerides (TG, ≥ 1.7 mmol/L). Multivariable robust Poisson logistic regression was used to estimate risk factors for MetS. The median age was 43 years at baseline, and 61.9% (n = 201) were female. The prevalences of abnormal FBG (12.8% vs. 25.9%), HDL-c (31.7% vs. 71.35%), WC (29.9% vs. 44.8%) and TG (8.9% vs. 45.2%) increased significantly between baseline and follow-up (p < 0.001 for all comparisons). Over a median follow-up of 43 months, the cumulative incidence of MetS was 38.8% (126/325: 95% confidence interval (CI) 33.4, 44.3). In multivariable analysis, factors positively associated with MetS were older age (incidence rate ratio (IRR) 1.02; 95%CI 1.01, 1.04), female sex (IRR 1.58; 95%CI 1.11, 2.24), DTG-based regimen use (IRR 1.50; 95%CI 1.01, 2.23) and higher body mass index (BMI) at enrollment (IRR 1.14; 95%CI 1.10, 1.18), while larger hip circumference (HC) was inversely associated (IRR 0.98; 95%CI 0.97, 0.99). The incidence of MetS was high among PWH and was significantly influenced by demographic, clinical and anthropometric factors. The results suggest a need for targeted screening, particularly among older persons, women, those with higher BMI, and potentially those using INSTI-based regimens. Longitudinal studies focusing on the mechanism through which INSTIs induce metabolic dysregulation and risk stratification are needed.