Effects of Pitavastatin on COVID-19 Incidence and Seriousness Among a Global Cohort of People With HIV

Markella V Zanni¹, Triin Umbleja², Carl J Fichtenbaum³, Kathleen V Fitch¹, Sara McCallum¹, Judith A Aberg⁴, Edgar Turner Overton⁵, Carlos D Malvestutto⁶, Gerald S Bloomfield⁷, Judith S Currier⁸, Samuel R Schnittman^{1

9}, Kristine M Erlandson¹⁰, Marissa R Diggs¹, Borek Foldyna¹¹, Esteban Martinez¹², Charurut Somboonwit¹³, Gary P Wang¹⁴, David Mushatt¹⁵, Elizabeth Connick¹⁶, Michael T Lu¹¹, Pamela S Douglas¹⁷, Heather J Ribaudo², Steven K Grinspoon¹

Affiliations

¹ Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
² Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Heath, Boston, Massachusetts, USA.
³ Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
⁴ Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁶ Division of Infectious Diseases, Ohio State University Medical Center, Columbus, Ohio, USA.
⁷ Department of Medicine, Duke Global Health Institute, and Duke Clinical Research Institute, School of Medicine, Duke University, Durham, North Carolina, USA.
⁸ Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁹ Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Division of Infectious Diseases, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
¹¹ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹² Infectious Diseases Service, Hospital Clinic and University of Barcelona, Barcelona, Spain.
¹³ Division of Infectious Diseases, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
¹⁴ Division of Infectious Diseases, School of Medicine, University of Florida, Gainesville, Florida, USA.
¹⁵ Division of Infectious Diseases, School of Medicine, Tulane University, New Orleans, Louisiana, USA.
¹⁶ Division of Infectious Diseases, College of Medicine, University of Arizona, Tucson, Arizona, USA.
¹⁷ Duke Clinical Research Institute, School of Medicine, Duke University, Durham, North Carolina, USA.

PMID: 39435321
PMCID: PMC11493083
DOI: 10.1093/ofid/ofae574

Clinical Trial

Effects of Pitavastatin on COVID-19 Incidence and Seriousness Among a Global Cohort of People With HIV

Markella V Zanni et al. Open Forum Infect Dis. 2024.

. 2024 Oct 10;11(10):ofae574.

doi: 10.1093/ofid/ofae574. eCollection 2024 Oct.

Authors

Affiliations

¹ Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
² Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Heath, Boston, Massachusetts, USA.
³ Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
⁴ Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁶ Division of Infectious Diseases, Ohio State University Medical Center, Columbus, Ohio, USA.
⁷ Department of Medicine, Duke Global Health Institute, and Duke Clinical Research Institute, School of Medicine, Duke University, Durham, North Carolina, USA.
⁸ Division of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁹ Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Division of Infectious Diseases, Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, Colorado, USA.
¹¹ Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹² Infectious Diseases Service, Hospital Clinic and University of Barcelona, Barcelona, Spain.
¹³ Division of Infectious Diseases, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
¹⁴ Division of Infectious Diseases, School of Medicine, University of Florida, Gainesville, Florida, USA.
¹⁵ Division of Infectious Diseases, School of Medicine, Tulane University, New Orleans, Louisiana, USA.
¹⁶ Division of Infectious Diseases, College of Medicine, University of Arizona, Tucson, Arizona, USA.
¹⁷ Duke Clinical Research Institute, School of Medicine, Duke University, Durham, North Carolina, USA.

PMID: 39435321
PMCID: PMC11493083
DOI: 10.1093/ofid/ofae574

Abstract

Background: Among people with HIV (PWH), COVID-19 is common and potentially severe. We leveraged REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) to assess the effects of statin therapy for cardiovascular disease prevention on COVID-19 outcomes (incidence and serious cases) among a global cohort of PWH.

Methods: COVID-19 data collection was implemented April 2020 to capture events from January 2020. COVID-19 was defined by positive test result or clinical diagnosis and serious COVID-19 according to the International Conference on Harmonisation definition. Among participants in follow-up on 1 January 2020, Cox proportional hazards modeling was used to estimate the hazard ratio (HR) of COVID-19 (pitavastatin/placebo), stratified by Global Burden of Disease region. Modification of statin effect following COVID-19 vaccination was evaluated via interaction with time-updated vaccination status.

Results: Among 6905 PWH, 32% were natal female and 41% were Black or African American. The median age was 53 years and the 10-year atherosclerotic cardiovascular disease risk score 4.5%. Statin therapy did not reduce COVID-19 incidence (HR, 1.05; 95% CI, .95-1.15) but appeared to reduce incidence of serious COVID-19 (HR, 0.75; 95% CI, .52-1.09). Among 1701 PWH with COVID-19, the relative risk (pitavastatin/placebo) for serious COVID-19 was 0.73 (95% CI, .52-1.03). The treatment effect size for serious COVID-19 fell within the hypothesized range, but the 95% CI crossed 1 given fewer-than-anticipated cases (117 vs 200). Furthermore, 83% reported COVID-19 vaccination by end of study, with a strong protective effect on serious COVID-19 (HR, 0.27; 95% CI, .14-.53; P < .0001). A protective statin effect was observed prior to vaccination.

Conclusions: Among PWH, statin therapy had no effect on COVID-19 incidence but showed potential to reduce risk of serious COVID-19 prior to COVID-19 vaccination.

Clinical trials registration: NCT02344290 (ClinicalTrials.gov).

Keywords: COVID-19; HIV; PWH; REPRIEVE; statin.

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Conflict of interest statement

Potential conflicts of interest. M. V. Z. reports grant support through her institution from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) and Gilead Sciences, Inc, relevant to the conduct of the study, as well as grants from NIH/NIAID and the NIH/National Heart, Lung, and Blood Institute (NHLBI); support for attending the Conference on Retroviruses and Opportunistic Infections and International Workshop for HIV and Women from conference organizing committee when abstract reviewer and/or speaker; and participation in a data and safety monitoring board for NIH funded studies, outside the submitted work. T. U. reports grants from NIH/NHLBI and Kowa Pharmaceuticals during the conduct of the study, as well as grants from NIH/NIAID and NIH/National Institute on Aging (NIA), outside the submitted work. C. J. F. reports research grants to his institution from Gilead Sciences, Merck, ViiV Healthcare and Moderna unrelated to this 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; personal fees for advisory boards from Glaxo Smith Kline/ViiV and Merck; and participation on a data and safety monitoring board for Kintor Pharmaceuticals, all outside the submitted work. 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 the submitted work. C. D. 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. S. C. reports consulting fees from Merck and Company and Resvirlogix, outside the submitted work. S. R. S. reports grant support through his institution from NIH/NIAID (T32 AI007387). K. M. E. reports grant support from NIH/NIA and Gilead Sciences, Inc; consulting fees paid to her institution from Gilead Sciences, Inc, ViiV Healthcare, and Janssen Therapeutics; and participation on an NIH data and safety monitoring board, all outside the submitted work. B. F. reports institutional research support from AstraZeneca, MedImmune, and MedTrace, as well as grants from NIH/NHLBI, all outside the submitted work. E. M. reports institutional research support from MSD and ViiV as well as honoraria for lectures or advisory boards from Gilead, Janssen, MDS, and ViiV. G. P. W. reports grant support through his institution from NIH/NIAID, NIH/National Institute of Diabetes and Digestive and Kidney Diseases, and Veterans Health Administration, all outside the submitted work. M. T. L. 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 the submitted work. H. J. R. 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 the submitted work. 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.

Figures

**Figure 1.**
Estimated pitavastatin effect on COVID-19 outcomes. ^aCause-specific hazard ratio (HR) estimates with 95% CIs from Cox proportional hazards models for time to first event, stratified by Global Burden of Disease region. Deaths without COVID-19 were treated as competing events and censored. In the supporting analyses while on treatment, treatment discontinuations were also treated as competing events and censored. For visual purposes, the HRs with 95% CIs are shown in log scale on the x-axis. 100PY, 100 person-years; IR, incidence rate.

See this image and copyright information in PMC

References

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Effects of Pitavastatin on COVID-19 Incidence and Seriousness Among a Global Cohort of People With HIV

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Effects of Pitavastatin on COVID-19 Incidence and Seriousness Among a Global Cohort of People With HIV

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Abstract

Conflict of interest statement

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