Switching HIV Regimens to Newer Drugs Tied to Weight Gain and Metabolic Risks in Large Chinese Cohort

Millions of people living with HIV now take antiretroviral therapy that suppresses the virus to undetectable levels, transforming what was once a fatal infection into a manageable chronic condition. As survival extends into decades, the long-term safety profile of treatment regimens has become as important as their antiviral potency. A new retrospective cohort study from China, published in BMC Infectious Diseases, adds substantial real-world evidence to an ongoing debate in HIV medicine: what happens to the body’s metabolism when patients move away from older drug combinations and onto the newer integrase strand transfer inhibitor, or INSTI, regimens that now dominate treatment guidelines worldwide.

The research team, led by Jingwei Tian and Yaokai Chen of Chongqing Public Health Medical Center together with collaborators at Zunyi Medical University and other Chinese institutions, followed 2,379 virologically suppressed people living with HIV for 144 weeks, nearly three years. All participants began the observation period on a classic first-line combination: tenofovir disoproxil fumarate plus lamivudine plus efavirenz, abbreviated TDF/3TC/EFV. This regimen served Chinese treatment programs for years, but it carries well-documented drawbacks, including kidney and bone toxicity from tenofovir disoproxil fumarate and central nervous system side effects from efavirenz. Some patients in the cohort continued on this older combination, while others switched to one of two modern alternatives: the single-tablet regimen bictegravir/emtricitabine/tenofovir alafenamide, known as BIC/FTC/TAF, or the two-drug combination dolutegravir plus lamivudine, known as DTG/3TC.

Because patients were not randomly assigned to their treatment paths, the investigators faced the fundamental challenge of any observational study: people who switch medications often differ systematically from those who do not. To address this, the team applied propensity score overlap weighting, a statistical technique that reweights the comparison groups so that baseline characteristics such as age, sex, body measurements, and laboratory values are balanced across them. This approach allows the analysis to approximate, though never perfectly replicate, the conditions of a randomized trial. The primary endpoint was the longitudinal change in body weight and body mass index from baseline to weeks 24, 48, 96, and 144. Secondary endpoints captured a broader metabolic picture, including changes in blood lipids, fasting blood glucose, the triglyceride-glucose index known as TyG, and serum uric acid.

The headline finding was unambiguous: weight and body mass index increased in every group over the 144 weeks, but the gains were markedly larger among those who switched to INSTI-based regimens. Patients moving to BIC/FTC/TAF gained more weight than those moving to DTG/3TC at weeks 24, 48, and 144, with the bictegravir-based regimen showing the steepest trajectory. This pattern echoes signals from international trials and cohort studies that have linked INSTI initiation and switching to clinically meaningful weight gain, but the Chinese data are particularly valuable because most prior evidence came from North American, European, and African populations, where baseline body composition and dietary patterns differ considerably.

The lipid results revealed a more nuanced picture. Compared with patients who stayed on TDF/3TC/EFV, both switch groups experienced increases in total cholesterol and low-density lipoprotein cholesterol, the fraction commonly labeled bad cholesterol because of its association with atherosclerotic cardiovascular disease. However, high-density lipoprotein cholesterol, the protective fraction, declined only in the BIC/FTC/TAF group, while triglycerides remained stable among those taking DTG/3TC. The direction of these changes matters clinically: a rise in LDL-C paired with a fall in HDL-C, as seen with bictegravir-based switching, shifts the lipid profile in a direction generally considered atherogenic, whereas the dolutegravir two-drug regimen appeared metabolically gentler on this front.

Beyond weight and lipids, the study tracked two additional metabolic markers that are gaining attention in HIV care. Fasting blood glucose rose in both switch groups, and serum uric acid also climbed in both, with significantly larger uric acid increases among patients on BIC/FTC/TAF. Elevated uric acid is the biochemical hallmark of hyperuricemia, the precursor state for gout, and has emerged as a recurrent finding in INSTI pharmacovigilance. The triglyceride-glucose index, a simple surrogate for insulin resistance calculated from fasting triglycerides and glucose, provided a window into early metabolic dysfunction without requiring formal glucose tolerance testing.

When the researchers translated these continuous laboratory changes into clinical diagnoses using multivariable Cox proportional hazards models, the differences between the two switch strategies became striking. Patients who switched to BIC/FTC/TAF faced more than double the hazard of developing overweight or obesity compared with those continuing the older regimen, with an adjusted hazard ratio of 2.47 and a 95 percent confidence interval of 1.96 to 3.10. They also carried a modestly elevated risk of dyslipidemia, at an adjusted hazard ratio of 1.18, and a substantially increased risk of hyperuricemia, at 2.23. The DTG/3TC group also fared worse than those who stayed on TDF/3TC/EFV, with adjusted hazard ratios of 1.56 for overweight or obesity and 1.76 for hyperuricemia, but the magnitude of risk was consistently lower than for the bictegravir-based triple-drug regimen. Notably, neither switch strategy significantly changed the risk of developing type 2 diabetes over the follow-up period.

The mechanistic story behind these observations remains incomplete, but several hypotheses circulate in the field. Integrase inhibitors may influence adipocyte biology and appetite regulation, potentially through effects on melanocortin signaling pathways, while the reversal of efavirenz-related toxicity could unmask baseline metabolic differences. Tenofovir alafenamide, the prodrug used in the BIC/FTC/TAF regimen, achieves high intracellular concentrations with lower plasma tenofovir exposure, sparing kidneys and bones, but some studies suggest it contributes more to weight gain than the older disoproxil fumarate salt. The uric acid signal may reflect changes in renal tubular handling as patients transition away from tenofovir disoproxil fumarate, which has mild uricosuric properties that lower serum urate. Disentangling drug-specific effects from the metabolic recovery that follows viral suppression and from the removal of older drugs remains one of the central analytical challenges in this literature.

For clinicians, the study’s practical message is one of vigilance rather than alarm. The authors emphasize that switching from TDF/3TC/EFV to either INSTI regimen was associated with significant increases in body weight and selected lipid parameters, and that BIC/FTC/TAF displayed a more pronounced adverse metabolic profile than DTG/3TC. They argue that metabolic monitoring after any switch to INSTI-based therapy deserves routine incorporation into HIV care, with particular attention for patients moving to bictegravir-based regimens. This is especially relevant in China and other Asian settings, where populations may have different baseline metabolic risk profiles and where the threshold at which weight gain becomes clinically consequential may differ from Western populations.

The study’s retrospective design imposes limits that the authors and the broader field acknowledge. Overlap weighting balances measured confounders but cannot account for unmeasured variables such as diet, physical activity, or the clinical reasons that prompted a switch in the first place. The 144-week horizon, while long by observational standards, may still underrepresent the cumulative metabolic burden of decades on therapy. Nevertheless, with 2,379 participants and nearly three years of longitudinal laboratory data, the analysis offers one of the clearest head-to-head real-world comparisons of these two widely used switch strategies in an Asian population. As INSTI regimens continue to displace older combinations globally, findings like these will shape how clinicians weigh the undeniable tolerability and convenience advantages of modern therapy against a metabolic cost that is now difficult to ignore.

Subject of Research: Long-term metabolic effects of switching from TDF/3TC/EFV to INSTI-based antiretroviral regimens in people living with HIV

Article Title: 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

Article References: Tian, J., Zhou, Y., Qin, Y., Lu, Y., Wang, Q., Liu, P., Kong, F., Harypursat, V., & Chen, Y. (2026). 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. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14425-w

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14425-w

Keywords: HIV, antiretroviral therapy, bictegravir, dolutegravir, tenofovir alafenamide, weight gain, dyslipidemia, hyperuricemia, integrase inhibitors, metabolic syndrome, cohort study, China