Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2025
DEFINE: A Prospective, Randomized, Phase 4 Trial to Assess a Protease Inhibitor-Based Regimen Switch Strategy to Manage Integrase Inhibitor-Related Weight Gain.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04442737 (A Phase 4, Randomized, Active-Controlled, Open-label Study to Evaluate the Safety and Tolerability of Switching to Once-Daily Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide), which is not on this map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 4, Randomized, Active-Controlled, Open-label Study to Evaluate the Safety and Tolerability of Switching to Once-Daily Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Fixed-dose Combination (FDC) Regimen in Virologically-suppressed Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Experiencing Rapid Weight Gain With an INI + TAF/FTC ARV Regimen
Who cites it
9 citing papers in PubMed.
- A 48-Week, Randomized Controlled Trial of Doravirine for Individuals With HIV and Obesity on Integrase Inhibitors and Tenofovir Alafenamide: The Do IT Study (ACTG A5391).Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Trial
- A crucial role for novel miR-12137-3p in supporting weight gain in treatment naïve HIV-infected patients on antiretroviral therapies.Journal of translational medicine · 2026Trial
- Weight gain and obesity management in people with HIV: pathophysiology, antiretroviral therapy effects, and clinical strategies.Topics in antiviral medicine · 2026Review
- To Switch or not to Switch: are there any Antiretroviral Strategies to Attenuate Weight Gain in People with HIV?Current HIV/AIDS reports · 2026Review
- Obesity and Weight Management in HIV: Epidemiology, Complications, and Emerging Treatments.Current HIV/AIDS reports · 2026Review
- Article
- Impact on weight of a Doravirine switch in people living with HIV.HIV medicine · 2026Article
- A United States HIV provider survey of antiretroviral therapy management in people living with HIV with co-occurring conditions.AIDS research and therapy · 2025Article
- Antiretroviral Therapy-Associated Weight Gain in Mexico, a Country Prone to Comorbidities.International journal of health policy and management · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundIntegrase strand transfer inhibitor (INSTI)-based antiretroviral (ARV) therapies have been associated with greater weight gain in people with human immunodeficiency virus (HIV) versus those on protease inhibitor (PI)-based regimens. The DEFINE study investigated whether switching from an INSTI- to a PI-based regimen could mitigate/reverse weight gain.
methodsDEFINE (NCT04442737) was a randomized, 48-week, open-label, prospective, phase 4 study in virologically suppressed adults with HIV-1 and ≥10% weight gain on INSTI + tenofovir alafenamide (TAF)/emtricitabine (FTC; <36 months prescreening). Participants either switched immediately to darunavir/cobicistat/FTC/TAF (D/C/F/TAF) or continued INSTI + TAF/FTC during weeks 0-24 then switched to D/C/F/TAF for weeks 24-48. The primary endpoint was least squares (LS) mean (95% confidence interval [CI]) percent weight change from baseline to week 24.
resultsOverall, 103 adults were randomized (D/C/F/TAF, n = 53; INSTI + TAF/FTC, n = 50); 30% were female, and 61% were Black/African American. No significant difference in weight change was observed at week 24 (LS mean change: D/C/F/TAF, 0.63% [95% CI, -.44% to 1.70%] vs INSTI + TAF/FTC, -0.24% [95% CI, -1.35% to .87%]; P = .24); however, a trend toward weight loss was observed with extended time post-ARV switch to D/C/F/TAF (baseline to week 48, -0.36% [95% CI, -1.77% to 1.06%]), particularly in subgroups at higher weight gain risk (eg, female and Black/African American participants). Metabolic endpoints paralleled weight change over time. D/C/F/TAF was well tolerated, with comparable virologic efficacy between arms.
conclusionsWhile no significant change in body weight was observed at 24 weeks after switching from INSTI + TAF/FTC to D/C/F/TAF among adults with weight gain, a trend toward weight loss emerged with longer time post-ARV switch, supporting further investigation of ARV selection/switch for weight management. Clinical Trials Registration. NCT04442737.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.