ArticleThe lancet. HIV2026
Risk of obesity, diabetes, hypertension, and major adverse cardiovascular events after a switch to an integrase inhibitor: a target trial emulation in REPRIEVE.
Article in The lancet. HIV, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The trial behind it
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Who cites it
4 citing papers in PubMed.
- Determinants of Metabolic Syndrome in Virally Suppressed People Living with HIV: A Single-Center Comparative Analysis of Antiretroviral Regimens.Metabolites · 2026Article
- Cardiovascular Disease Risk with Integrase Inhibitor-based Antiretroviral Therapy: A Causal Inference Analysis in RESPOND.Open forum infectious diseases · 2026Article
- Beyond HIV: investigating key drivers of metabolic syndrome in midlife women with HIV in the INSTI era.AIDS research and therapy · 2026Article
- Residual HIV activity and host immunometabolic remodeling during antiretroviral therapy: implications for cardiovascular-kidney-metabolic risk.Frontiers in immunology · 2026Review
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Authors and funding
28 authors.
Funding
Abstract
backgroundIntegrase strand-transfer inhibitors (INSTIs) are linked to weight gain, but data on their cardiometabolic effects, particularly major adverse cardiovascular events (MACE), are scarce. We aimed to estimate the risk of obesity, diabetes, hypertension, and MACE after switching to an INSTI in people with HIV at low-to-moderate cardiovascular risk.
methodsIn this retrospective cohort study, we used data from the global Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) to emulate a series of trials comparing switching to an INSTI versus remaining on a non-INSTI regimen on risk of incident obesity, diabetes, hypertension, and MACE. The REPRIEVE trial collected data across 12 countries from participants aged 40-75 years, on a stable antiretroviral therapy regimen for at least 6 months, with a CD4 count of >100 cells per μL, and with low-to-moderate risk for atherosclerotic cardiovascular disease. From this cohort, we included participants without a previous diagnosis of the outcomes or previous INSTI use and used data for a follow-up period of 5 years, until the outcome event, loss to follow-up, death, or study end. Data from emulated trials were pooled and hazard ratios (HRs) were estimated with weighted Cox proportional hazard models, accounting for competing events.
findings5114 participants met eligibility criteria for at least one emulated trial, representing 99 357 person-trials (median age 49 years [45-54]; 62 826 [63·2%] of 99 357 were male; 36 531 [36·8%] were female). 2981 (58·3%) of 5114 participants were captured as an INSTI switcher in at least one trial. Most switchers (2412 [80·9%] of 2981) initiated a dolutegravir-based regimen and most (47 263 [67·1%] of 70 458) non-switchers were on an efavirenz-based regimen. The HR of obesity (HR 1·41, 95% CI 1·22-1·59), diabetes (1·50, 1·24-1·81), and hypertension (1·45, 1·26-1·67) was higher in switchers than non-switchers. We did not observe an effect on MACE (1·17, 0·87-1·57).
interpretationThe increase in cardiometabolic risk profile suggests long-term observation of people with HIV switching to INSTIs will be crucial to ensure appropriate management of comorbidities and to assess for future development of MACE.
fundingNational Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare.
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