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Clinical Trial
. 2025 Feb;12(2):e118-e129.
doi: 10.1016/S2352-3018(24)00276-5. Epub 2025 Jan 17.

Performance of the pooled cohort equations and D:A:D risk scores among individuals with HIV in a global cardiovascular disease prevention trial: a cohort study leveraging data from REPRIEVE

Steven K Grinspoon  1 , Markella V Zanni  2 , Virginia A Triant  3 , Amy Kantor  4 , Triin Umbleja  4 , Marissa R Diggs  5 , Sarah M Chu  5 , Kathleen V Fitch  5 , Judith S Currier  6 , Gerald S Bloomfield  7 , José L Casado  8 , Mireia de la Peña  9 , Lori E Fantry  10 , Edward Gardner  11 , Judith A Aberg  12 , Carlos D Malvestutto  13 , Carl J Fichtenbaum  14 , Michael T Lu  15 , Heather J Ribaudo  4 , Pamela S Douglas  16
Affiliations
Clinical Trial

Performance of the pooled cohort equations and D:A:D risk scores among individuals with HIV in a global cardiovascular disease prevention trial: a cohort study leveraging data from REPRIEVE

Steven K Grinspoon et al. Lancet HIV. 2025 Feb.

Abstract

Background: Risk estimation is an essential component of cardiovascular disease prevention among people with HIV. We aimed to characterise how well atherosclerotic cardiovascular disease (ASCVD) risk scores used in clinical guidelines perform among people with HIV globally.

Methods: In this prospective cohort study leveraging REPRIEVE data, we included participants aged 40-75 years, with low-to-moderate traditional cardiovascular risk, not taking statin therapy. REPRIEVE participants were enrolled from sites in 12 countries across Global Burden of Disease Study (GBD) regions. We assessed the performance of the pooled cohort equations (PCE) risk score for ASCVD and the data-collection on adverse effects of anti-HIV drugs (D:A:D) risk score. We calculated C statistics, observed-to-expected (OE) event ratios, and Greenwood-Nam-D'Agostino goodness-of-fit (GND) statistics, overall and in subgroups by race, sex, and GBD regions (clustering low-income and middle-income countries and high-income countries). We did a recalibration for PCE risk score among people with HIV in high-income countries. REPRIEVE was registered with ClinicalTrials.gov, NCT02344290.

Findings: We included 3893 participants, recruited between March 26, 2015, and July 31, 2019. The median age was 50 years (IQR 45-55), with 2684 (69%) male and 1209 (31%) female participants. 1643 (42%) were Black or African American, 1346 (35%) participants were White, 566 (15%) were Asian, and 338 (9%) were recorded as other race. Overall, discrimination of the PCE risk score was moderate (C statistic 0·72 [95% CI 0·68-0·76]) and calibration was good (OE event ratio 1·11; GND p=0·87). However, calibration suggested overprediction of risk in low-income and middle-income countries and corresponding underprediction in high-income countries. When restricted to high-income countries, we found underprediction (OE event ratio >1·0) among women (2·39) and Black or African American participants (1·64). Findings were similar for the D:A:D risk score (C statistic 0·71 [0·65-0·77]; OE event ratio 0·89; p=0·68). Improved calibration of the PCE risk score in high-income countries was achieved by multiplying the original score by 2·8 in Black or African American women, 2·6 in women who were not Black or African American, and 1·25 in Black or African American men.

Interpretation: Among the global cohort of people with HIV in REPRIEVE, the PCE risk score underpredicted cardiovascular events in women and Black or African American men in high-income countries and overpredicted cardiovascular events in low-income and middle-income countries. Underprediction in subgroups should be considered when using the PCE risk score to guide statin prescribing for cardiovascular prevention among people with HIV in high-income countries. Additional research is needed to develop risk scores accurate in predicting ASCVD among people with HIV in low-income and middle-income countries.

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

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Conflict of interest statement

Declaration of interests SKG reports grant support through his institution from the 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. MVZ reports grant support through her institution from the NIH/National Institute of Allergy and Infectious Diseases (NIAID) and Gilead Sciences, relevant to the conduct of the study, as well as grants from the NIH/NIAID and the NIH/National Heart, Lung, and Blood Institute (NHLBI); support for attending the Conference on Retroviruses and Opportunistic Infections and the International Workshop for HIV and Women from the conference organising committee when she served as an abstract reviewer and/or speaker; and participation in the DSMB for NIH-funded studies, outside the submitted work. VAT reports grants from the NIH/National Institute of Aging (NIA) and NIH/NHLBI, outside of the submitted work. AK reports grants from NIH/NIAID, NIH/NHLBI, NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and NIH/NIA, outside of the submitted work. TU reports grants from NIH/NHLBI and Kowa Pharmaceuticals during the conduct of the study, as well as grants from NIH/NIAID and NIH/NIA, outside the submitted work. JSC reports consulting fees from Merck and Company and Resvirlogix, outside the submitted work. JLC reports honoraria for presentations for Gilead, MSD, and ViiV, and honoraria from Gilead Sciences for Advisory Board membership, all outside the submitted work. EG reports institutional research support for clinical trials from Gilead Sciences and ViiV Healthcare. JAA reports grants from Massachusetts General Hospital during the conduct of the study; institutional research support for clinical trials from Emergent Biosolutions, Gilead Sciences, Glaxo Smith Kline, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare; personal fees for advisory boards from Glaxo Smith Kline/ViiV, Invivyd, Merck and Regeneron; and participation on the DSMB for Kintor Pharmaceuticals, all outside the submitted work. CDM reports institutional research support by 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 the 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, the 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/NIDDK, and NIH/NIA, outside of the submitted work. All other authors declare no competing interests.

References

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