ACTG Presents Important Findings from REPRIEVE at CROI 2025

Presentations Address Frailty, Inflammation, Asymptomatic Heart Muscle Damage, and Mental Function

LOS ANGELES, March 12, 2025 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, today presented findings from the REPRIEVE trial about the use of statins among people living with HIV with frailty and the relationship between major adverse cardiovascular events (MACE) and measurements of inflammation and asymptomatic heart muscle damage. These results were shared in two oral abstracts: “Frailty is Associated with Higher MACE Incidence but Does Not Appear to Modify Pitavastatin Effects” and “Plaque, Inflammation, Subclinical Myocardial Injury and MACE in the REPRIEVE Mechanistic Substudy” at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco, California.

REPRIEVE (The Randomized Trial to Prevent Vascular Events in HIV) 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.

“We are eager to share data from REPRIEVE at CROI about the relationship between frailty and major cardiovascular events, the importance of inflammation and asymptomatic heart muscle damage, and the impact of statin therapy on neurocognition (mental function) and heart failure risk,” said ACTG Chair Joseph J. Eron, M.D., University of North Carolina. “REPRIEVE was a groundbreaking study that has informed a multitude of international guidelines, which now recommend statins to prevent cardiovascular disease in many people living with HIV and we expect that it will continue to generate meaningful findings that improve the care of people living with HIV.”

Frailty is Associated with Higher MACE Incidence but Does Not Appear to Modify Pitavastatin Effects
Today’s presentation examined whether frailty is associated with MACE among people living with HIV and whether statins may prevent MACE across a spectrum of frailty. Researchers found that higher levels of frailty were associated with increased risk of MACE among participants. They also determined that while adults living with HIV and frailty were routinely under-prescribed key preventive therapies such as statins, frailty status did not appear to modify the protective effects of pitavastatin that were seen in the primary trial.

While further research is needed, the study concluded that incorporating frailty assessments such as the frailty index may help identify people living with HIV who are at risk of MACE.

“The strong association in this analysis between the age-related syndrome of frailty and major adverse cardiovascular events may suggest similar underlying mechanisms and, further, that screening for frailty can help identify the participants at highest risk for cardiovascular events,” said Presenting Author Kristine Erlandson, M.D., University of Colorado Anschutz Medical Campus. “While providers and patients may question the added benefit of statins in patients with numerous comorbidities, the data presented today support the use of pitavastatin among adults living with HIV and frailty.”

Plaque, Inflammation, Subclinical Myocardial Injury and MACE in the REPRIEVE Mechanistic Substudy
This secondary analysis presented today assessed for the first time the relationship between coronary plaque and measurements of inflammation and asymptomatic heart muscle damage with MACE. Today’s presentation demonstrated that among participants in REPRIEVE’s mechanistic substudy, individuals with noncalcified coronary plaque (buildup of plaque in the arteries that can cause a heart attack) and higher blood levels of inflammation and heart muscle injury at study entry were at higher risk of having a cardiovascular event over six years of follow up even though they did not have symptoms. In exploratory analyses, plaque and biomarker (blood proteins associated with cardiovascular disease) combinations further improved the accuracy of predicting the risk of MACE beyond traditional risk scores. The data also suggested that the benefit of pitavastatin to prevent MACE may be greater among individuals who have noncalcified coronary plaque and evidence of low-grade myocardial damage, which may precede symptoms. Additional investigation is necessary to determine how pitavastatin can be most effective for these individuals.  

“These data suggest that key plaque, inflammatory, and asymptomatic heart muscle damage markers are strongly related to MACE, even among people living with HIV who are not experiencing cardiac-related symptoms,” said Presenting Author and Study Chair Steven Grinspoon, M.D, Harvard Medical School and Massachusetts General Hospital.

“These data highlight the need for additional studies to identify people living with HIV who might benefit most from statin therapy and to identify new mechanistic pathways to target,” said REPRIEVE Mechanistic Substudy Protocol Chair and Lead Author Michael Lu, M.D., M.P.H., Harvard Medical School and Massachusetts General Hospital.

ACTG also presented two posters at CROI reporting on additional REPRIEVE findings:

• No Evidence of a Detrimental Effect of Pitavastatin on Neurocognitive Function Among People with HIV found no evidence to suggest that pitavastatin impacted neurocognitive function among people living with HIV at low to moderate cardiovascular disease risk, even among those who entered the study with some existing level of impairment.

  “Concerns about potential detrimental cognitive effects of statins are often raised when considering statin therapy,” said Presenting Author Dr. Erlandson. “The results from this randomized, blinded study, which show no relationship between statin therapy and change in neurocognitive function, should provide reassurance to patients and providers.”

• Heart Failure Risk and Events In People with HIV: The Randomized Trial To Prevent Vascular Events In HIV (REPRIEVE)” (Gerald Bloomfield, et al.) found that the number of heart failure events among people living with HIV in REPRIEVE was consistent with the low estimated PREVENT (Predicting Risk of Cardiovascular Disease Events) heart failure risk rates. Participants who were Black, female, lived in sub-Saharan Africa, had pre-existing hypertension, and/or elevated body mass were more likely to experience heart failure.

REPRIEVE began in 2015 as cooperative agreements (HL12339, HL123336, HL164284, and HL164285) and was a collaborative effort between the National Institutes of Health’s 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 Dr. Lu, 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, ACTG
RLReiss@mednet.ucla.edu