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Randomized Controlled Trial
. 2025 Apr;12(4):e261-e272.
doi: 10.1016/S2352-3018(24)00345-X.

Statin effects on the incidence of major non-cardiovascular disease events among a global cohort of people with HIV: a randomised controlled trial

Marissa R Diggs  1 , Triin Umbleja  2 , Sara McCallum  1 , Markella V Zanni  1 , Sarah M Chu  1 , Kathleen V Fitch  1 , Gerald S Bloomfield  3 , Judith S Currier  4 , Esteban Martinez  5 , Philip E Castle  6 , Aya Awwad  1 , Mamta K Jain  7 , Roger Bedimo  7 , Bronwyn Hendricks  8 , Jose Narrea  9 , Vincente Estrada  10 , Jorge Pinto  11 , Judith A Aberg  12 , Carlos D Malvestutto  13 , Carl J Fichtenbaum  14 , Michael T Lu  15 , Heather J Ribaudo  2 , Pamela S Douglas  16 , Steven K Grinspoon  17
Affiliations
Randomized Controlled Trial

Statin effects on the incidence of major non-cardiovascular disease events among a global cohort of people with HIV: a randomised controlled trial

Marissa R Diggs et al. Lancet HIV. 2025 Apr.

Abstract

Background: Given the pleiotropic effects of statins beyond lipid-lowering, statins might positively impact other, non-cardiovascular diseases (non-CVDs). In this study, we prospectively assessed statin effects on non-CVD events and their incidence among people with HIV globally.

Methods: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE; ClinicalTrials.gov, NCT02344290) was a randomised, placebo-controlled trial of pitavastatin for CVD prevention took place from 2015 to 2023 at 145 research sites in 12 countries and is completed. In this analysis of prespecified secondary outcomes of REPRIEVE, we assessed effects of pitavastatin 4 mg daily (vs placebo) on major non-CVD events (including AIDS-defining events, non-AIDS-defining cancers, renal disease, and liver disease) and the Strategic Timing of Antiretroviral Treatment (START) trial outcome (a collective measure of morbidity including CVD among people with HIV) using Cox proportional hazards regression, stratified by sex and CD4 cell count.

Findings: Among the 7769 people with HIV enrolled (3888 in the pitavastatin group and 3881 in the placebo group), 6402 participants completed the study (3201 in each group). Over a median 5·6 years (IQR 4·7-6·3) of follow-up, the incidence of major non-CVD events was 9·17 per 1000 person-years in the pitavastatin group and 9·90 per 1000 person-years in the placebo group (hazard ratio [HR], cause-specific: 0·92, 95% CI 0·76-1·13; p=0·44). The incidence of the START outcome was 15·2 per 1000 person-years in the pitavastatin and 18·3 per 1000 person-years in the placebo group (HR 0·83, 95% CI 0·71-0·97; p=0·016), driven by the effect on CVD. In the placebo group, incidences of the non-AIDS-defining cancer and CVD components of the START Trial outcome were highest (5·83 per 1000 person-years and 5·48 per 1000 person-years) whereas AIDS-defining events were less frequent (3·60 per 1000 person-years), and varied across global regions. With pitavastatin, the incidence of CVD was lower compared with placebo (3·36 per 1000 person-years), however non-AIDS-defining cancers remained high (5·40 per 1000 person-years). Non-AIDS-defining cancers were the leading cause of mortality for both groups.

Interpretation: Among a global cohort of people with HIV, treatment with pitavastatin showed no major reduction in non-CVD events, including non-AIDS-defining cancers. These findings outline the limitations of statin therapy for the prevention of non-CVD, highlighting the need for other strategies for such events.

Funding: National Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare.

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Conflict of interest statement

Declaration of interests TU reports grants from National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) and Kowa Pharmaceuticals during the conduct of the study, as well as grants from NIH/National Institute of Allergy and Infectious Diseases (NIAID) and NIH/National Institute on Aging (NIA), outside the submitted work. MVZ reports grant support through her institution from NIH/NIAID and Gilead Sciences, relevant to the conduct of the study, as well as grants from NIH/NIAID and NIH/NHLBI; support for attending Conference on Retroviruses and Opportunistic Infections and International Workshop for HIV and Women from the conference organising committee; and participation in the Data and Safety Monitoring Board for NIH funded studies, outside the submitted work. JSC reports consulting fees from Merck and Resvirlogix, outside the submitted work. EM has received honoraria for lectures or advisory boards from Gilead, Janssen, MSD, and ViiV, and his institution has received research grants from MSD and ViiV, all outside the submitted work. PEC reports affiliation with the National Cancer Institute. MKJ reports grant support from Cancer Prevention and Research Institute of Texas and Gilead Sciences and research support for clinical trials from AbbVie, Laurent, Merck, GSK/ViiV, NIH/NHLBI, and NIH/NIAID, all outside the submitted work. RB reports consulting fees for ad hoc scientific advisory boards from Merck, ViiV Healthcare, Gilead Sciences, Theratechnologies, Janssen, and Shionogi, all outside of the submitted work. VE reports financial support from Gilead, ViiV, and Johnson & Johnson Innovative Medicines, all outside the submitted work. JP reports institutional research grant support from NIH, Janssen, Gilead Sciences, and ViiV Healthcare, and personal fees for advisory boards from GSK/ViiV, all outside the submitted work. JAA reports institutional research support for clinical trials from Emergent Biosolutions, Gilead Sciences, GSK, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare and personal fees for advisory boards from GSK/ViiV and Merck; and participation on Data and Safety Monitoring Board for Kintor Pharmaceuticals, all outside the submitted work. CDM reports institutional research support from Lilly and honoraria from ViiV Healthcare, Gilead Sciences, and Pfizer for advisory board membership, all outside the submitted work. CJF reports research grant support through his institution from Gilead Sciences, ViiV Healthcare, GSK, and Merck, all outside the submitted work. MTL reports grant support through his institution from NIH/NHLBI and Kowa Pharmaceuticals America for the conduct of the study. He also reports research support to his institution from the American Heart Association, AstraZeneca, Ionis, Johnson & Johnson Innovation, MedImmune, the National Academy of Medicine, NIH/NHLBI, and the Risk Management Foundation of the Harvard Medical Institutions Incorporated, outside of the submitted work. HJR reports grants from Kowa Pharmaceuticals during the conduct of the study, as well as grants from NIH/NIAID, NIH/NHLBI, NIH/National Institute of Diabetes and Digestive and Kidney Diseases, and NIH/NIA, outside of the submitted work. SKG reports grant support through his institution from NIH, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare for the conduct of the study; personal fees from Theratechnologies and ViiV; and service on the Scientific Advisory Board of Marathon Asset Management, all outside the submitted work All other authors declare no competing interests.

References

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