Longitudinal analysis of metabolic changes in people with HIV on integrase inhibitor-based versus efavirenz-based therapy: a prospective real-world cohort study in China

Abstract Background Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended for HIV treatment but has been associated with metabolic adverse effects. However, real-world longitudinal data on these metabolic changes remain limited. This study aimed to characterize weight gain, dyslipidemia, and hepatic steatosis in ART-naïve people living with HIV (PLWH) initiating INSTI-based versus efavirenz (EFV)-based therapy. Methods This prospective cohort study enrolled 772 participants at Nanfang Hospital, Southern Medical University from 2020 to 2023. Participants were categorized into 3 groups: EFV/tenofovir disoproxil fumarate (TDF)/lamivudine (3TC) (n = 389); elvitegravir/cobicistat (EVG/c)/tenofovir alafenamide (TAF)/emtricitabine (FTC) or bictegravir (BIC)/TAF/FTC (n = 168); and dolutegravir (DTG)/3TC or DTG/3TC/TDF (n = 215). Metabolic parameters—including body mass index (BMI), lipids, and hepatic steatosis assessed via controlled attenuation parameter (CAP)—were evaluated at baseline, 6, 12, and 24 months using generalized estimating equations. Results At 24 months, INSTI-based regimens were associated with significantly higher BMI compared to EFV/TDF/3TC (all P < 0.001), with no difference between INSTI subtypes. All groups showed early increases in triglycerides (TG) and total cholesterol (TC) that stabilized after 12 months; TG and TC levels at 24 months did not differ significantly between TAF-containing INSTI regimens and other groups. The prevalence of hepatic steatosis (CAP ≥ 238 dB/m) peaked at 31.2% at year 1 and declined to 28.8% at year 2. Multivariate analysis identified higher BMI (OR 1.55, 95% CI 1.44–1.67; p < 0.001), elevated TG (OR 1.44, 95% CI 1.22–1.70; p < 0.001), and elevated LDL-C (OR 1.90, 95% CI 1.21–2.98; p = 0.005) as independent risk factors. Conclusion INSTI-based ART was associated with sustained weight gain but did not worsen long-term dyslipidemia compared to an EFV-based regimen in a real-world setting. Hepatic steatosis correlated with metabolic parameters rather than INSTI exposure.