Long-term metabolic changes after switching from TDF/3TC/EFV to BIC/FTC/TAF or DTG/3TC in people living with HIV: a retrospective comparative cohort study in China

The metabolic consequences of switching from tenofovir disoproxil fumarate + lamivudine + efavirenz (TDF+3TC + EFV) to newer integrase strand transfer inhibitor (INSTI)-based regimens remain incompletely characterized, particularly among Chinese populations. This study compared 144-week metabolic changes associated with switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) versus dolutegravir/lamivudine (DTG/3TC) in virologically suppressed Chinese people living with HIV (PLWH). This retrospective cohort study included virologically suppressed Chinese PLWH who either continued TDF+3TC + EFV or switched to BIC/FTC/TAF or DTG/3TC. Propensity score overlap weighting (OW) was applied to balance baseline covariates. The primary endpoint was the longitudinal change in body weight and BMI from baseline to weeks 24, 48, 96, and 144. Secondary endpoints included changes in lipid profiles, fasting blood glucose (FBG), the triglyceride-glucose (TyG) index, and uric acid (UA). Cox proportional hazards models were used to compare incident outcomes. A total of 2,379 individuals were included. Over 144 weeks, weight and BMI increased in all groups, with greater gains in those switching to BIC/FTC/TAF or DTG/3TC; BIC/FTC/TAF showed higher gains than DTG/3TC at weeks 24, 48, and 144. Compared with TDF+3TC + EFV, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increased in both switch groups, while high-density lipoprotein cholesterol (HDL-C) declined only in BIC/FTC/TAF; triglycerides (TG) remained stable in DTG/3TC. FBG and UA levels rose in both switch groups, with larger UA increases in BIC/FTC/TAF. Multivariable Cox regression showed that BIC/FTC/TAF was associated with higher hazards of overweight/obesity (aHR 2.47 [1.96–3.10]), dyslipidemia (aHR 1.18 [1.04–1.35]), and hyperuricemia (aHR 2.23 [1.83–2.71]), while DTG/3TC increased risks of overweight/obesity (aHR 1.56 [1.03–2.35]) and hyperuricemia (aHR 1.76 [1.32–2.35]). No significant differences were observed in type 2 diabetes. In this real-world cohort study, switching from TDF+3TC + EFV to BIC/FTC/TAF or DTG/3TC was associated with significant increases in body weight and selected lipid parameters. BIC/FTC/TAF showed a more pronounced adverse metabolic profile. These findings highlight the importance of metabolic monitoring after switching to INSTI-based regimens, particularly for patients switching to BIC/FTC/TAF.