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Randomized Controlled Trial
. 2025 Feb 24;80(2):425-433.
doi: 10.1093/cid/ciae422.

Pitavastatin Is Well-Tolerated With no Detrimental Effects on Physical Function

Kristine M Erlandson  1 , Triin Umbleja  2 , Heather J Ribaudo  2 , Jennifer A Schrack  3 , Edgar T Overton  4   5 , Carl J Fichtenbaum  6 , Kathleen V Fitch  7 , Jhoanna C Roa  8 , Marissa R Diggs  7 , Kenneth Wood  9 , Markella V Zanni  7 , Gerald S Bloomfield  10 , Carlos Malvestutto  11 , Judith A Aberg  12 , Maria C Rodriguez-Barradas  13   14 , Rosalba Gomez Morones  13   14 , Katherine Breaux  13   14 , Pamela S Douglas  15 , Steven K Grinspoon  7 , Todd T Brown  16
Affiliations
Randomized Controlled Trial

Pitavastatin Is Well-Tolerated With no Detrimental Effects on Physical Function

Kristine M Erlandson et al. Clin Infect Dis. .

Abstract

Background: Little is known about the potential benefits or harms of statins on physical function among people with human immunodeficiency virus (PWH).

Methods: REPRIEVE was a double-blind randomized controlled trial evaluating pitavastatin for primary prevention of major adverse cardiovascular events in PWH. Time to complete 10 chair rises, 4-m gait speed, grip strength, and a modified short physical performance test were assessed annually for up to 5 years in the ancillary study PREPARE and analyzed using linear mixed models.

Findings: Of 602 PWH, 52% were randomized to pitavastatin and 48% to placebo. Median age was 51 years; 18% were female at birth; 2% transgender; and 40% Black, and 18% Hispanic. Median PREPARE follow-up was 4.7 (4.3-5.0) years. Muscle symptoms (grade ≥3 or treatment-limiting) occurred in 5% of both groups. There was no evidence of decline in chair rise rate in either treatment group and no difference in the pitavastatin group compared to placebo (estimated difference -0.10 [95% confidence interval, -.30 to 0.10] rises/min/year; P = .31). Small declines over time were observed in other physical function tests in both treatment groups, with no apparent differences between groups.

Interpretation: We observed minimal declines in physical function over 5 years of follow-up among middle-aged PWH, with no differences among PWH randomized to pitavastatin compared to placebo. This finding, combined with low prevalence of myalgias, supports the long-term safety of statin therapy on physical function, when used for primary prevention of major adverse cardiovascular events among PWH.

Trial registration: ClinicalTrials.gov NCT02344290 NCT03070223.

Keywords: HIV; frailty; muscle; physical function; statin.

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Conflict of interest statement

Potential conflicts of interest. K. M. E. has received research funding from the NIH/NIA in support of the present manuscript; outside of the current work, she has received research funding from Gilead Sciences and has consulted for Gilead Sciences, ViiV Pharmaceuticals, and Merck, all to her institution. T. U. reports funding to her institution in support of the present manuscript from NIH/NIA and NIH/NHLBI, and grant funding to her institution outside of the submitted work from NIH/NIAID and Kowa Pharmaceuticals. H. J. R. 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. J. A. S. is a consultant for Edwards Lifesciences and serves on the advisory board of BellSant, Inc. E. T. O. reports grant support from Gilead Sciences, ViiV Healthcare, and Janssen, consulting fees from ViiV Healthcare, and employment with ViiV Healthcare Medical Affairs, all outside of the submitted work. C. J. F. reports research grants to his institution from Gilead Sciences, Merck, ViiV Healthcare, and Moderna unrelated to this work. K. V. F.: No conflicts to declare. J. C. R.: No conflicts to declare. M. R. D.: No conflicts to declare. K. W.: No conflicts to declare. M. V. Z. reports grant support through her institution from NIH/NIAID and Gilead Sciences, Inc., relevant to the conduct of the study, as well as grants from NIH/NIAID and NIH/NHLBI; support for attending CROI and International Workshop for HIV and Women from conference organizing committee when abstract reviewer and/or speaker; and participation in DSMB for NIH-funded studies, outside the submitted work. G. S. B.: No conflicts to declare. C. M. reports institutional research support by Lilly and honoraria from ViiV Healthcare, Gilead Sciences, and Pfizer for advisory board membership, all outside the submitted work. J. A. A. reports institutional research support for clinical trials from Emergent Biosolutions, Gilead Sciences, Glaxo Smith Kline, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare and personal fees for advisory boards from Glaxo Smith Kline/ViiV and Merck; and participation on DSMB for Kintor Pharmaceuticals, all outside the submitted work. M. C. R.-B.: No conflicts to declare. R. G. M.: No conflicts to declare. K. B.: No conflicts to declare. P. S. D.: No conflicts to declare. S. K. G. reports grant support through his institution from NIH, Kowa Pharmaceuticals America, Inc., Gilead Sciences, Inc., 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. T. T. B.: No conflicts to declare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Pitavastatin effect on physical function. A, Annualized rate of change in physical function (rate of change per year) within each treatment group. B, Treatment effect on physical function estimated as difference in annualized rate of change (pitavastatin vs placebo) from linear mixed models. The estimates and 95% CIs are shown in the original scale in the axis table. For visual purposes, they are plotted in the standardized scale representing change per year in standard deviations of the outcome measure. “Chair rise rate (rises/min), prospective” is limited to the participants enrolled prospectively (ie, those with pretreatment physical function measurements available). Abbreviations: CI, confidence interval; obs, number of observations across participants; ref, reference; SPPB, short physical performance battery.
Figure 2.
Figure 2.
Pitavastatin effect on chair rise rate within prespecified subgroups. A, Annualized rate of change in chair rise rate within prespecified subgroups by baseline characteristics. B, Treatment effect within subgroups estimated as difference in annualized rate (pitavastatin vs placebo) from linear mixed models. P values are from type 3 tests for interaction between time, treatment group, and subgroup variable (ie, the difference in the rate of change over time [slope] between pitavastatin and placebo groups between the levels of the subgroup variable). Baseline SPPB is limited to participants with pretreatment physical function measurements available. Presence of preexisting muscle ache or weakness is defined as grade 1 or higher muscle weakness or aches at baseline by participant self-report. Abbreviations: CI, confidence interval; obs, number of observations across participants; ref, reference; SPPB, short physical performance battery.
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References

    1. Chou R, Dana T, Blazina I, Daeges M, Jeanne TL. Statins for prevention of cardiovascular disease in adults: evidence report and systematic review for the US preventive services task force. JAMA 2016; 316:2008–24. - PubMed
    1. Morofuji Y, Nakagawa S, Ujifuku K, et al. Beyond lipid-lowering: effects of statins on cardiovascular and cerebrovascular diseases and cancer. Pharmaceuticals (Basel) 2022; 15:151. - PMC - PubMed
    1. Shah ASV, Stelzle D, Lee KK, et al. Global burden of atherosclerotic cardiovascular disease in people living with HIV: systematic review and meta-analysis. Circulation 2018; 138:1100–12. - PMC - PubMed
    1. Grinspoon SK, Fitch KV, Zanni MV, et al. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med 2023; 389:687–99. - PMC - PubMed
    1. Grinspoon SK, Ribaudo HJ, Douglas PS. Trial update of pitavastatin to prevent cardiovascular events in HIV infection. N Engl J Med 2024; 390:1626–8. - PMC - PubMed

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