CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

853

Time-Updated Win Ratio Aligns With Primary REPRIEVE Findings and Suggests Early Pitavastatin Benefit Emma Davies Smith 1 , Pamela Douglas 2 , Sara McCallum 3 , James Troendle 4 , Marissa Diggs 3 , Sarah Chu 3 , Michael T. Lu 3 , Markella V. Zanni 3 , Steven Grinspoon 3 , Heather Ribaudo 1 1 Harvard TH Chan School of Public Health, Boston, MA, USA, 2 Duke Clinical Research Institute, Durham, NC, USA, 3 Massachusetts General Hospital, Boston, MA, USA, 4 National Institutes of Health, Bethesda, MD, USA Background: REPRIEVE demonstrated a 36% reduction in the hazard of major adverse cardiovascular (CV) events (MACE) among those randomized to pitavastatin vs placebo using a time-to-first-event (TTFE) analysis. TTFE results can be difficult to interpret with CV composite endpoints, as “less severe” events (MI and stroke) are likely to precede “more severe” events (death). Win ratio analysis is gaining traction in CV trials as an intuitive alternative that incorporates event severity, but has been criticized for dependence on follow-up time, as more severe events occur with longer follow-up. We performed a win ratio analysis of REPRIEVE and assessed trends over time. Methods: All pairs consisting of one participant from each arm are constructed. MACE components are then compared in order of severity until it can be determined which participant did better. Here, a participant “wins” if their event/censor time is greater than their comparator’s event time. The ratio of pitavastatin to placebo wins estimates the win ratio (WR), with WR > 1 suggesting pitavastatin benefit. The WR was estimated for MACE (event tier 1: Death due to CV or undetermined causes > 2: stroke > 3: MI > 4: other CV event including transient ischemic attack, unstable angina and peripheral arterial ischemia > 5: CV procedure), and Hard MACE (1: CV death > 2: stroke > 3: MI). To investigate time-dependence, administrative censoring was performed at each of 8 follow-up years. Results: At year 1, arms contributed equally to ordered wins on CV death and procedures (Figure). Pitavastatin had an apparent advantage on stroke and MI, while placebo had an apparent advantage on less severe CV events. As a result, the WR for Hard MACE (1.59) was larger than that of MACE (1.18). After year 1, pitavastatin steadily gained advantage over placebo on all events. Event tier contributions stabilized by approximately year 4, and the WR for MACE and Hard MACE were consistently estimated as 1.55 (95% CI: 1.20 to 1.99) and 1.65 (95% CI: 1.20 to 2.27) respectively, for years 6 through 8. Conclusions: Time-updated win ratios suggest effects of pitavastatin are early and persistent for CV death, stroke, and MI. Less severe CV events and procedures contributed little to win effects. The reciprocal of the win ratio at 8 years (WR=1.55) is approximately the TTFE hazard ratio (HR=0.64). Our win ratio analysis agrees with REPRIEVE’s primary findings, and provides more insight into the protections of pitavastatin against severe CV events among people with HIV.

852

Low-Density Lipoprotein Changes in People With HIV Initiating Statins for Primary Prevention Thibaut Davy-Mendez 1 , Sonia Napravnik 1 , Carol E. Golin 1 , Joseph J. Eron 1 , Stephen A. Berry 2 , April C. Pettit 3 , Greer Burkholder 4 , Joseph A. Delaney 5 , Mari Kitahata 5 , Edward Cachay 6 , George Yendewa 7 , Kenneth Mayer 8 , Richard Moore 9 , Katerina Christopoulos 10 , Ross J. Simpson 1 , for the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 The Johns Hopkins University, Baltimore, MD, USA, 3 Vanderbilt University Medical Center, Nashville, TN, USA, 4 University of Alabama at Birmingham, Birmingham, AL, USA, 5 University of Washington, Seattle, WA, USA, 6 University of California San Diego, La Jolla, CA, USA, 7 Case Western Reserve University, Cleveland, OH, USA, 8 The Fenway Institute, Boston, MA, USA, 9 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 10 University of California San Francisco, San Francisco, CA, USA Background: Statin use will likely increase in persons with HIV (PWH) at low-to-moderate CVD risk given the cardiovascular disease (CVD) prevention benefit demonstrated by the REPRIEVE trial. However, real-world benefit of statins may be lower than expected with insufficient low-density lipoprotein (LDL) reductions. Older studies reported that few PWH on statins experienced timely LDL reductions, but more recent evidence is needed. We examined LDL changes among PWH initiating statins for primary prevention in a clinical cohort at 8 US sites. Methods: We included PWH without CVD who had a first statin prescription between 2014 and 2022 (baseline). In intention-to-treat analyses ignoring statin therapy changes and discontinuations, we estimated (1) the mean 1-year change (absolute and relative) in LDL from baseline using generalized estimating equations, and (2) the 1-year cumulative incidence of an LDL reduction ≥30% from baseline using Kaplan Meier curves. Secondary analyses were stratified by baseline LDL and statin intensity. Person-time was censored at death, loss to follow-up (12 months with no HIV visit or lab), or data end date, whichever occurred first. We used multiple imputation for PWH missing baseline LDL values (17%). Results: We included 4334 PWH (80% men, 46% Black, 41% white). At baseline, median age was 54 years (IQR 47, 59), median CD4 count 638 cells/µL (417, 905), median LDL 125 mg/dL (97, 153), 25% had diabetes mellitus, and 92% had a viral load <200 copies/mL. The most commonly prescribed initial statins were atorvastatin (64%), pravastatin (16%), and rosuvastatin (16%). At 6 sites with dosage data (N=2979), 8%, 72%, and 21% initiated low-, medium-, and high-intensity statin therapy, respectively. After 1 year, among all PWH, the mean absolute change in LDL was -33.5 mg/dL (95% CI -35.2, -31.9), or a relative change of -21.8% (95% CI -23.0%, -20.6%), and 35.5% (95% CI 34.0%, 37.0%) of PWH had an LDL reduction ≥30% (Table 1). PWH with higher baseline LDL and those initiating higher-intensity statin therapy had greater LDL reductions and cumulative incidence of LDL reduction ≥30% at 1 year (Table 1). Conclusions: In this US sample of PWH initiating statins, about one-third overall and 60% of those with high baseline LDL had a 1-year LDL reduction ≥30%. Efforts are needed to elucidate and address drivers of inadequate LDL reductions among PWH, which may include patient non-adherence, lack of statin dose up-titration, and true statin non-response despite adherence.

Poster Abstracts

854

HIV-Superinfection in Kidney Transplant Recipients With HIV Who Received Organs From Donors With HIV Grace Rozek 1 , Yolanda Eby 1 , Diane Brown 1 , Darin Ostrander 1 , Craig Martens 2 , Sarah E. Benner 1 , Feben Habtehyimer 1 , Dorry L. Segev 3 , Christine M. Durand 1 , Aaron A. R. Tobian 1 , Andrew D. Redd 2 , for the HOPE in Action Investigators 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 National Institute of Allergy and Infectious Diseases, Baltimore, MD, USA, 3 New York University Langone Medical Center, New York, NY, USA Background: The HIV Organ Policy Equity (HOPE) Act allows for transplantation of kidneys from donors with HIV to recipients with HIV (HIV D+/R+) in the

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