ACTG, a global clinical trials network focused on HIV and other infectious diseases, today presented data demonstrating that switching to an integrase inhibitor-based antiretroviral regimen increased the risk of weight gain and cardiometabolic complications over the next five years compared to remaining on a regimen without an integrase inhibitor. They did not find an increased risk of major adverse cardiovascular events (MACE), such as heart attacks or strokes. These results from the REPRIEVE (The Randomized Trial to Prevent Vascular Events in HIV) study were shared as the late breaking poster presentation, “Risk of Obesity, Cardiometabolic Disease and MACE after Switch to an Integrase Inhibitor in REPRIEVE” at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco, California.

REPRIEVE was the first large-scale clinical trial to test a primary prevention strategy to reduce the increased risk of cardiovascular disease among people living with HIV. It found that participants who took pitavastatin calcium (a daily statin pill that lowers cholesterol) reduced their risk of MACE by 36 percent compared with those receiving a placebo over a median duration of five years of follow up.

“This analysis from REPRIEVE provides an in-depth evaluation of the metabolic effects of switching to an integrase inhibitor,” said ACTG Chair Joseph J. Eron, M.D., University of North Carolina. “While a number of prior studies have reported disproportionate weight gain among people living with HIV who initiated treatment with an integrase inhibitor, this is one of the few that has evaluated people who were taking other HIV treatments and followed them for more than two years after switching to an integrase inhibitor.”

Today’s presentation estimated the effect of switching to an integrase inhibitor-based regimen on obesity, diabetes, hypertension, metabolic syndrome, and MACE among participants in REPRIEVE. This analysis included 2,708 study participants who switched to an integrase inhibitor-containing regimen, 82 percent of which included dolutegravir.

Among participants who switched to an integrase inhibitor-based regimen compared to those who did not, researchers estimated an increased risk of developing obesity [hazard ratio (HR): 1.32, 95% confidence interval (CI): 1.07-1.47], diabetes (HR: 1.38, 95% CI: 1.10-1.69), hypertension (HR: 1.38, 95% CI: 1.13, 1.61), and metabolic syndrome (HR: 1.15, 95% CI: 1.00-1.31). They did not find an increased risk of MACE (HR: 1.03, 95% CI: 0.63, 1.52). Researchers noted that it will be important for future studies to determine whether taking integrase inhibitors leads to cardiovascular disease (including heart attacks and strokes) over the long-term, and to investigate potential cardiometabolic mechanisms.

“The risk of cardiometabolic complications associated with integrase inhibitors was small in this study,” said Senior Author and Study Chair Steven Grinspoon, M.D., Harvard Medical School. “However, given that rates of obesity, diabetes, hypertension, and metabolic syndrome increased following a switch to an integrase inhibitor-based regimen, and that these are all important contributors to cardiovascular disease risk, individuals on integrase inhibitor-containing regimens should be closely monitored for cardiometabolic complications over the long term.”

REPRIEVE began in 2015 as cooperative agreements (HL12339, HL123336, HL164284, and HL164285) and was a collaborative effort between the National Institutes of Health’s (NIH) National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID), two of the largest NIH institutes, and ACTG (AI068636). It received additional funding from the NIH Office of AIDS Research, Kowa Pharmaceuticals America, Inc. (providers of pitavastatin calcium and placebo), Gilead Sciences, Inc., and ViiV HealthCare.

The study is led by Dr. Grinspoon and Pamela S. Douglas, M.D., Duke University School of Medicine (Co-chair), who led the Clinical Coordinating Center and Heather Ribaudo, Ph.D., Harvard School of Public Health (Lead Statistician) and Michael Lu, M.D., M.P.H., Harvard Medical School and Massachusetts General Hospital (Protocol Chair, Mechanistic Substudy of REPRIEVE), who led the Data Coordinating Center. ACTG is led by Dr. Eron and Rajesh T. Gandhi, M.D., Massachusetts General Hospital and Harvard Medical School (ACTG Vice-Chair).

To learn more, please visit www.reprievetrial.org.

About ACTG ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve.

Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH.

Media Contact:Rachel Reiss, ACTGRLReiss@mednet.ucla.edu