Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults (REPRIEVE)

Randomized Trial to Prevent Vascular Events in HIV - REPRIEVE

People with HIV are at risk for cardiovascular disease (CVD). This study evaluated the use of pitavastatin to reduce the risk of CVD in adults with HIV on antiretroviral therapy (ART).

The REPRIEVE trial consisted of two parallel identical protocols:

• REPRIEVE (A5332) was funded by the NHLBI, with additional infrastructure support provided by the NIAID, and was conducted in U.S and select international sites (approximately 120 sites in 11 countries).
• REPRIEVE (EU5332) was co-sponsored by NEAT ID and MGH, and was conducted at 13 sites in Spain.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; HIV
• Intervention / Treatment: Drug: Pitavastatin; Drug: Placebo

Detailed Description

There are few strategies to prevent CVD in people with HIV (PWH), even though they are at high risk for developing CVD. Statin medications are used to lower cholesterol and may be effective at reducing the risk of CVD in PWH. The purpose of this study was to evaluate the use of pitavastatin to reduce the risk of CVD in PWH on ART.

This study enrolled PWH who were on any ART regimen (ART was not provided by the study) for at least 6 months before study entry and were at low to moderate risk of CVD using the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline thresholds for recommended statin initiation.

Participants were randomly assigned to receive 4 mg of pitavastatin or placebo once a day for their entire study duration. Pitavastatin or placebo could be discontinued and clinically indicated statin therapy initiated at the discretion of the site investigator or the participant's care provider, with the intention of following the participant according to the intention-to-treat trial design. Study visits occurred at study entry and Months 1 and 4. Starting at Month 4, study visits occurred every 4 months for the rest of the study. Depending on when participants enrolled, they were in the study for a total of 4 to 8 years. Study visits included medical and medication history reviews, physical examinations, blood collections, assessments and questionnaires, urine collections (for some participants), and an electrocardiogram (ECG) (at study entry only).

Participants at US sites had the option of enrolling in a substudy (Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers: Mechanistic Substudy of REPRIEVE [A5333s]). The substudy evaluated the effect of pitavastatin on the progression of non-calcified coronary atherosclerotic plaque (NCP) and inflammatory biomarkers in PWH. Participants in the substudy attended study visits at study entry and Months 4 and 24. The visits included questionnaires and assessments, a blood collection, and a coronary computed tomography angiography (CCTA). The Mechanistic Substudy closed to accrual on February 6, 2018, when its accrual target of 800 participants had been reached. Sites that enrolled participants into the Mechanistic Substudy are indicated with asterisk (*) at the end of the institution names in the Contacts and Locations section.

Participants enrolled in REPRIEVE from select study sites, including international sites, through December, 2017, were included in the REPRIEVE Kidney Function Objectives Cohort to evaluate the effects of pitavastatin on parameters of kidney function in the setting of HIV. These objectives include evaluating high risk groups and mechanisms driving kidney function decline in the setting of HIV.

Women and men enrolled in REPRIEVE after February, 2016 were included in an observational cohort (REPRIEVE Women's Objectives Cohort) facilitating assessment of sex-specific mechanisms of CVD risk and risk reduction among PWH. This effort also included an evidence-based recruitment campaign to enhance women's participation in REPRIEVE.

In response to the SARS-CoV-2 pandemic, a supplemental objective was added in 2020. To better understand how COVID-19 affects PWH and if pitavastatin may reduce the risk of serious COVID-19 disease, we evaluated interrelated but independent key topics including epidemiology, host factors, and protective strategies. Starting from April 2020, COVID-19 assessment was completed at each study visit, and blood was collected for COVID-19 biomarkers.

The data and safety monitoring board (DSMB) recommended stopping the trial for efficacy at the second planned review on March 30, 2023, and concluded that no unexpected safety concerns had been reported. Following the DSMB action, participants were asked to return for the final study visit. All final visits were completed by August 21, 2023. We here present the results based on the final trial database, including the full follow-up out to closeout visits.

• Study Type: Interventional
• Enrollment (Actual): 7769
• Phase: Phase 3

Contacts and Locations

Study Locations

• Botswana
  • South-East District
    • Gaborone, South-East District, Botswana
      • Gaborone CRS
• Brazil
  • Rio de Janeiro, Brazil, 21040-360
    • Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
  • Rio de Janeiro, Brazil, 20020-000
    • Projeto Praça Onze Pesquisa em Saúde CRS
  • Rio de Janeiro, Brazil, 20221-903
    • Hospital Federal dos Servidores do Estado CRS
  • São Paulo, Brazil, 01246-900
    • Instituto de Infectologia Emilio Ribas CRS
  • São Paulo, Brazil, 05403-010
    • Centro de Pesquisas Clínicas IC-HCFMUSP CRS
  • Amazonas
    • Manaus, Amazonas, Brazil, 69040000
      • Tropical Medicine Foundation Dr. Heitor Vieira Dourado CRS
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • School of Medicine, Federal University of Minas Gerais CRS
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao CRS
  • Rio de Janeiro
    • Nova Iguaçu, Rio de Janeiro, Brazil, 26030-380
      • HGNI HIV Family Care Clinic - HHFCC CRS
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04121-000
      • Centro de Referencia e Treinamento DST/AIDS CRS
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Vancouver ID Research & Care Centre Society CRS
  • Ontario
    • Hamilton, Ontario, Canada, L8S 1A4
      • Hamilton Health Sciences - Special Immunology Services Clinic CRS
    • Toronto, Ontario, Canada, M5G 1K2
      • Maple Leaf Research CRS
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital CRS
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Chronic Viral Illness Service CRS
    • Québec, Quebec, Canada, G1V 4G2
      • Centre hospitalier de l'Université Laval CRS
• Haiti
  • Port-au-Prince, Haiti, HT-6110
    • Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
  • Port-au-Prince, Haiti, HT-6110
    • GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
• India
  • Maharashtra
    • Pune, Maharashtra, India, 411001
      • Byramjee Jeejeebhoy Medical College (BJMC) CRS
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600113
      • Chennai Antiviral Research and Treatment (CART) CRS
• Peru
  • Lima, Peru, 15063
    • Barranco CRS
  • Lima, Peru, 32 - 15088
    • San Miguel CRS
• Puerto Rico
  • PR
    • San Juan, PR, Puerto Rico, 00935
      • Puerto Rico AIDS Clinical Trials Unit CRS*
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1862
      • Soweto ACTG CRS
    • Johannesburg, Gauteng, South Africa, 2092
      • Wits Helen Joseph Hospital CRS (Wits HJH CRS)
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4052
      • Durban International Clinical Research Site CRS
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7700
      • University of Cape Town Lung Institute (UCTLI) CRS
    • Tygerberg, Western Cape, South Africa, 7505
      • Famcru Crs
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Badalona, Spain, 080916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08907
    • Hospital Universitario de Bellvitge
  • Barcelona, Spain, 08003
    • Hospital Universitario Valle d'Hebron
  • Bilbao, Spain, 48013
    • Hospital Universitario de Basurto de Basurto
  • Elche, Spain, 03203
    • Hospital General Universitario de Elche
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos
  • Madrid, Spain, 28007
    • Hospital Gregorio Universitario Maranon
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
• Thailand
  • Bangkok, Thailand, 10330
    • Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
  • Chiang Mai, Thailand, 50200
    • Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
• Uganda
  • Kampala, Uganda
    • Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Alabama CRS*
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona CRS
  • California
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research CRS
    • Los Angeles, California, United States, 90073
      • VA West Los Angeles Medical Center CRS
    • Los Angeles, California, United States, 90232
      • Los Angeles LGBT Center CRS
    • Los Angeles, California, United States, 90033-1079
      • University of Southern California CRS*
    • Los Angeles, California, United States, 90035
      • UCLA CARE Center CRS*
    • Palm Springs, California, United States, 92264
      • Eisenhower Health Center at Rimrock CRS
    • Palo Alto, California, United States, 94304-5350
      • Stanford AIDS Clinical Trials Unit CRS
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center CRS*
    • San Francisco, California, United States, 94110
      • Ucsf Hiv/Aids Crs*
    • Torrance, California, United States, 90502
      • Harbor-UCLA CRS*
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital CRS*
    • Denver, Colorado, United States, 80204
      • Denver Public Health CRS
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University CRS
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System CRS
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20005
      • Whitman-Walker Health CRS
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University CRS (GU CRS)
    • Washington D.C., District of Columbia, United States, 20036
      • Capital Medical Associates, PC CRS
    • Washington D.C., District of Columbia, United States, 20422
      • Infectious Diseases Clinic, Washington DC Veterans Affairs Medical Center CRS
  • Florida
    • Gainesville, Florida, United States, 32610
      • Malcom Randall VA Medical Center CRS
    • Miami, Florida, United States, 33136
      • The University of Miami AIDS Clinical Research Unit (ACRU) CRS
    • Miami, Florida, United States, 33133
      • AHF-The Kinder Medical Group CRS
    • Miami, Florida, United States, 33136
      • University of Miami Infectious Disease Research Unit at Jackson Memorial Hospital CRS
    • Miami, Florida, United States, 33140
      • AHF - South Beach CRS
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center CRS
    • Sarasota, Florida, United States, 34237
      • Community AIDS Network/Comprehensive Care Clinic CRS
    • Tampa, Florida, United States, 33602
      • Florida Department of Health - Hillsborough County
    • Vero Beach, Florida, United States, 32960
      • AIDS Research and Treatment Center of the Treasure Coast CRS
  • Georgia
    • Atlanta, Georgia, United States, 30308-2012
      • The Ponce de Leon Center CRS
    • Augusta, Georgia, United States, 30912
      • Augusta University Research Institute, Inc. CRS
  • Illinois
    • Chicago, Illinois, United States, 60612
      • UIC Project WISH CRS
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS*
    • Chicago, Illinois, United States, 60612
      • Rush University CRS*
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Infectious Diseases Research CRS
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Department of Internal Medicine, University of Iowa Hospitals & Clinics CRS
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Bluegrass Care Clinic/University of Kentucky Research Foundation CRS
    • Louisville, Kentucky, United States, 40202
      • 550 Clinic -University of Louisville CRS
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane - Louisiana Community AIDS Research Program (T-LaCARP) CRS
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University CRS*
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center CRS
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center CRS
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital CRS (MGH CRS)*
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS*
    • Springfield, Massachusetts, United States, 01199
      • Baystate Infectious Diseases Clinical Research CRS
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hosp. CRS
    • Southfield, Michigan, United States, 48075
      • St. John Newland Medical Associates CRS
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital CRS
  • Mississippi
    • Jackson, Mississippi, United States, 39213
      • University of Mississippi Medical Center CRS
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Washington University Therapeutics (WT) CRS*
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • Specialty Care Center CRS
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Univ. Hosp. CRS
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School Clinical Research Center CRS*
  • New York
    • New York, New York, United States, 10010
      • VA New York Harbor Healthcare System (NYHHS), NY Campus CRS
    • New York, New York, United States, 10029
      • Infectious Disease Clinical and Translational Research Center (CTRC) CRS
    • New York, New York, United States, 10003
      • Mount Sinai Beth Israel CRS*
    • New York, New York, United States, 10010
      • Weill Cornell Chelsea CRS*
    • New York, New York, United States, 10011
      • Mount Sinai Downtown CRS*
    • New York, New York, United States, 10019
      • Mount Sinai West Samuels CRS*
    • New York, New York, United States, 10025
      • Mount Sinai St. Luke's Morningside CRS*
    • New York, New York, United States, 10032-3732
      • Columbia P&S CRS*
    • New York, New York, United States, 10065
      • Weill Cornell Uptown CRS*
    • Rochester, New York, United States, 14642
      • University of Rochester Adult HIV Therapeutic Strategies Network CRS*
    • The Bronx, New York, United States, 10468
      • James J Peters VA Medical Center CRS
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Chapel Hill CRS*
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center CRS
    • Greensboro, North Carolina, United States, 27401
      • Greensboro CRS*
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center CRS
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Cincinnati Clinical Research Site*
    • Cleveland, Ohio, United States, 44106
      • Case Clinical Research Site*
    • Columbus, Ohio, United States, 43210
      • Ohio State University CRS*
    • Toledo, Ohio, United States, 43614
      • University of Toledo Medical Center CRS
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74127
      • Oklahoma State University Center for Health Sciences CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Division of Infectious Diseases Clinical Research Center- Drexel University CRS
    • Philadelphia, Pennsylvania, United States, 19140
      • Center of Translational AIDS Research, Lewis Katz School of Medicine at Temple University CRS
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Therapeutics, CRS*
    • Pittsburgh, Pennsylvania, United States, 15212
      • Positive Health Clinic CRS
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh CRS*
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital Clinical Research Site (TMH CRS) CRS*
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina: Division of Infectious Diseases CRS
    • Columbia, South Carolina, United States, 29209
      • Prisma Health CRS
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Therapeutics (VT) CRS*
  • Texas
    • Dallas, Texas, United States, 75208
      • Trinity Health and Wellness Center CRS
    • Dallas, Texas, United States, 75216
      • Dallas VA Medical Center CRS
    • Dallas, Texas, United States, 75235-9173
      • UT Southwestern HIV/ID Clinical Trials Unit CRS
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VAMC REPRIEVE CRS
    • Houston, Texas, United States, 77030
      • Houston AIDS Research Team CRS*
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Heart and Vascular Institute CRS
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University CRS
  • Washington
    • Seattle, Washington, United States, 98104-9929
      • University of Washington AIDS CRS*
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin, Inc. CRS
• Zimbabwe
  • Harare, Zimbabwe
    • Milton Park CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individual with HIV-1
• Combination antiretroviral therapy (ART) for at least 180 days prior to study entry
• CD4+ cell count greater than 100 cells/mm^3

• Acceptable screening laboratories including:

  • Fasting low-density lipoprotein (LDL) cholesterol as follows:

    • If ASCVD risk score was less than 7.5%, LDL cholesterol must have been less than 190 mg/dL.
    • If ASCVD risk score was greater than or equal to 7.5% and less than or equal to 10%, LDL must have been less than 160 mg/dL.
    • If ASCVD risk score was greater than 10% and less than or equal to 15%, LDL must have been less than 130 mg/dL.
    • Participants with LDL less than 70 mg/dL were eligible regardless of the 10-year ASCVD risk score, in line with the ACC/AHA 2013 Prevention Guidelines.
  • Fasting triglycerides less than 500 mg/dL
  • Hemoglobin greater than or equal to 8 g/dL for female participants and greater than or equal to 9 g/dL for male participants
  • Glomerular filtration rate (GFR) greater than or equal to 60 mL/min/1.73m^2 or creatinine clearance (CrCl) greater than or equal to 60 mL/min
  • Alanine aminotransferase (ALT) less than or equal to 2.5 x the upper limit of normal (ULN)
• For persons with known chronic active hepatitis B or C, calculated fibrosis 4 score (FIB-4) must have been less than or equal to 3.25
• Ability and willingness of participant or legal representative to provide written informed consent

Exclusion Criteria:

• Clinical ASCVD, as defined by 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, including a previous diagnosis of any of the following:

  • Acute myocardial infarction (AMI)
  • Acute coronary syndromes
  • Stable or unstable angina
  • Coronary or other arterial revascularization
  • Stroke
  • Transient ischemic attack (TIA)
  • Peripheral arterial disease presumed to be of atherosclerotic origin
• Current diabetes mellitus with LDL greater than or equal to 70 mg/dL
• 10-year ASCVD risk score estimated by Pooled Cohort Equations greater than 15%
• Active cancer within 12 months prior to study entry, except successfully treated non-melanomatous skin cancer and Kaposi sarcoma without visceral organ involvement
• Known decompensated cirrhosis
• History of myositis or myopathy with active disease in the 180 days prior to study entry
• Known untreated symptomatic thyroid disease
• History of allergy or severe adverse reaction to statins
• Use of specific immunosuppressants or immunomodulatory agents including but not limited to tacrolimus, sirolimus, rapamycin, mycophenolate, cyclosporine, tumor necrosis factor (TNF)-alpha blockers or antagonists, azathioprine, interferon, growth factors, or intravenous immunoglobulin (IVIG) in the 30 days prior to study entry.
• Current use of erythromycin, colchicine, or rifampin
• Use of any statin drugs, gemfibrozil, or PCSK9 inhibitors in the 90 days prior to study entry
• Current use of an investigational new drug that would be contraindicated
• Serious illness or trauma requiring systemic treatment or hospitalization in the 30 days prior to study entry
• Current pregnancy or breastfeeding
• Alcohol or drug use that, in the opinion of the site investigator, would interfere with completion of study procedures
• Other medical, psychiatric, or psychological condition that, in the opinion of the site investigator, would interfere with completion of study procedures and or adherence to study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pitavastatin; Participants received pitavastatin once a day for the entire time they were in study follow-up.	Drug: Pitavastatin; One tablet (4 mg) taken once daily, orally with or without food
Placebo Comparator: Placebo; Participants received placebo for pitavastatin once a day for the entire time they were in study follow-up.	Drug: Placebo; One tablet taken once daily, orally with or without food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of Major Adverse Cardiovascular Event (MACE)	MACE is a composite of cardiovascular (CV) death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack (TIA), peripheral arterial ischemia, coronary, carotid or peripheral arterial revascularization, or death from an undetermined cause. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Non-CV deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of Cardiac Ischemia or Myocardial Infarction	Cardiac ischemia or myocardial infarction component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Cerebrovascular Event (Stroke or TIA)	Cerebrovascular event (stroke or TIA) component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Peripheral Arterial Ischemia	Peripheral arterial ischemia component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Death From CV Causes	CV death component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Non-CV deaths and deaths from undetermined causes were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Death From CV or Undetermined Causes	CV or undetermined death component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Non-CV deaths were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Cardiac Catheterization or Revascularization	Cardiac cardiac catheterization or revascularization component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Carotid or Cerebrovascular Revascularization	Carotid or cerebrovascular revascularization component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Peripheral Arterial Revascularization	Peripheral arterial revascularization component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of MACE or Death	A composite outcome including MACE and death from any cause. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Death (All-cause)	Death from any cause. The incidence rates were estimated based on time to event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Non-CV Clinical Diagnoses	A composite of non-CV clinical diagnoses including: non-AIDS-defining cancers (excluding basal cell and squamous cell carcinomas of the skin), AIDS-defining events (based on Centers for Disease Control and Prevention [CDC] 2014 classification), end-stage renal disease, and end-stage liver disease. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Non-AIDS-defining Cancer	Non-AIDS-defining cancer (excluding basal cell and squamous cell carcinomas of the skin) component of the composite non-CV clinical diagnoses outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of AIDS-defining Event	AIDS-defining event component of the composite non-CV clinical diagnoses outcome. Events were captured based on the Centers for Disease Control and Prevention [CDC] 2014 classification. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of End-Stage Renal Disease	End-stage renal disease (defined as initiation of dialysis or renal transplantation) component of the composite non-CV clinical diagnoses outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of End-Stage Liver Disease	End-stage liver disease (defined as cirrhosis or hepatic decompensation requiring hospitalization) component of the composite non-CV clinical diagnoses outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Non-fatal Serious Adverse Event	Safety analysis outcome measure of non-fatal serious adverse event was defined by International Conference on Harmonisation (ICH) criteria. Fatal events were excluded as deaths were a secondary efficacy outcome (see outcome measure: incidence rate of death (all-cause)). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Diabetes	Safety analysis outcome measure of diabetes was defined as new diagnosis of diabetes with initiation of anti-diabetic agent. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Myalgia, Muscle Weakness or Myopathy	Safety analysis outcome measure of myalgia, muscle weakness or myopathy which were grade 3 or higher or treatment-limiting. Grade 3 or higher includes grade 3 and 4 events, where grade 3 refers to severe and grade 4 to life-threatening according to DAIDS AE Grading Table (version 2.1). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Rhabdomyolysis	Safety analysis outcome measure of rhabdomyolysis which was grade 3 or higher or treatment-limiting. Grade 3 or higher includes grade 3 and 4 events, where grade 3 refers to severe and grade 4 to life-threatening, according to DAIDS AE Grading Table (version 2.1). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo). Due to small number of events, there was no adjustment for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Grade 3 or Higher ALT	Safety analysis outcome measure of Grade 3 or higher alanine transaminase (ALT). Grade 3 or higher includes grade 3 and 4 events, where grade 3 refers to severe and grade 4 to life-threatening, according to DAIDS AE Grading Table (version 2.1). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo). Due to small number of events, there was no adjustment for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Adverse Event (AE)	Safety analysis outcome measure of any AE. AE collection included events of grade ≥3, those that were serious (defined by International Conference on Harmonisation (ICH) criteria) or treatment-limiting, and targeted diagnosis of diabetes. Grade ≥3 includes events that were grade 3 (serious) or grade 4 (life-threatening) per DAIDS AE Grading Table (version 2.1). Fatal events were excluded as deaths were a secondary efficacy outcome (see outcome measure: incidence rate of death (all-cause)). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Fasting Low-density Lipoprotein Cholesterol (LDL-C)	LDL-C level was derived as LDL-C calculated according to the Friedewald formula at triglycerides ≤400 mg/dL, and direct LDL-C at triglycerides >400 to <500 mg/dL. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	At entry and months 12, 24, 36, 48, 60, 72, 84. Participants' follow-up time on study varied, depending on their time of enrollment.
Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	Non-HDL cholesterol levels were calculated as total cholesterol minus HDL cholesterol. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	At entry and months 12, 24, 36, 48, 60, 72, 84. Participants' follow-up time on study varied, depending on their time of enrollment.
Incidence Rate of Serious COVID-19	Serious COVID-19 was defined as COVID-19 that resulted in hospitalization or death or was life-threatening as per the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline E2A definition. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for GBD region to account for regional differences. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From January 1, 2020 through end of study; the median follow-up time was 3.3 years.
Incidence Rate of COVID-19	COVID-19 was defined as COVID-19 clinical diagnosis or positive test result (SARS-CoV-2 PCR or rapid antigen tests). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios (prescribed pitavastatin compared to placebo) from Poisson regression models, adjusted for GBD region to account for regional differences. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	From January 1, 2020 through end of study; the median follow-up time was 3.3 years.
For Mechanistic Substudy: Change in Non-Calcified Plaque (NCP) Volume From Baseline to Year 2	NCP was defined as plaque voxels with attenuation of <350. Change in NCP is expressed as absolute change from baseline (calculated as NCP volume at 2 years minus NCP volume at entry), based on quantitative read of the CT scan, whenever available. Participants without a quantitative read and no evidence of NCP based on the corresponding qualitative read were assigned a value of zero for the change. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	Entry and Year 2.
For Mechanistic Substudy: Number of Participants With Progression of NCP From Baseline to Year 2	Progression at Year 2 was defined as any progression/increase in NCP volume in participants with evidence of NCP at entry, or incident NCP in participants without evidence of NCP at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	Entry and year 2.
For Mechanistic Substudy: Change in Total Plaque Volume From Baseline to Year 2	Total plaque includes all plaque voxels (noncalcified + calcified). Change in total plaque volume is expressed as absolute change from baseline (calculated as volume at 2 years minus volume at entry). Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	Entry and year 2.
For Mechanistic Substudy: LpPLA2 Level	Level of inflammatory biomarker lipoprotein-associated phospholipase A2 (LpPLA2). Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	Entry and month 24.
For Mechanistic Substudy: Change in LpPLA2 From Baseline	Change in inflammatory biomarker LpPLA2 from baseline calculated as value at month 24 minus value at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	Entry and month 24.
For Mechanistic Substudy: HsCRP Level	Level of inflammatory marker high-sensitivity C-reactive protein (HsCRP). Censored values below or above the assay limit were imputed. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	Entry and month 24.
For Mechanistic Substudy: Change in HsCRP From Baseline	Change in inflammatory biomarker hsCRP from baseline calculated as value at month 24 minus value at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	Entry and month 24.
For Mechanistic Substudy: Soluble CD163 Level	Level of immune biomarker soluble CD163. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	Entry and month 24.
For Mechanistic Substudy: Change in Soluble CD163 From Baseline	Change in immune biomarker soluble CD163 from baseline calculated as value at month 24 minus value at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).	Entry and month 24.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of MACE by Sex	Subgroup analysis of the primary composite MACE outcome measure (as described above) by sex. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The Cox proportional hazards models described for the primary outcome above were expanded to include sex and interaction of sex and treatment, to evaluate modification of statin effect.	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of MACE by Race	Subgroup analysis of the primary composite MACE outcome measure (as described above) by race. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The Cox proportional hazards models described for the primary outcome above were expanded to include race and interaction of race and treatment, to evaluate modification of statin effect.	From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Massachusetts General Hospital; National Heart, Lung, and Blood Institute (NHLBI); Gilead Sciences; NEAT ID Foundation; Kowa Pharmaceuticals America, Inc.
• Investigators: Study Chair: Steven Grinspoon, MD, Harvard Medical School (HMS and HSDM)

Publications and helpful links

General Publications

• Umbleja T, Brown TT, Overton ET, Ribaudo HJ, Schrack JA, Fitch KV, Douglas PS, Grinspoon SK, Henn S, Arduino RC, Rodriguez B, Benson CA, Erlandson KM. Physical Function Impairment and Frailty in Middle-Aged People Living With Human Immunodeficiency Virus in the REPRIEVE Trial Ancillary Study PREPARE. J Infect Dis. 2020 Jul 9;222(Suppl 1):S52-S62. doi: 10.1093/infdis/jiaa249.
• Zanni MV, Fitch K, Rivard C, Sanchez L, Douglas PS, Grinspoon S, Smeaton L, Currier JS, Looby SE. Follow YOUR Heart: development of an evidence-based campaign empowering older women with HIV to participate in a large-scale cardiovascular disease prevention trial. HIV Clin Trials. 2017 Mar;18(2):83-91. doi: 10.1080/15284336.2017.1297551.
• Grinspoon SK, Fitch KV, Overton ET, Fichtenbaum CJ, Zanni MV, Aberg JA, Malvestutto C, Lu MT, Currier JS, Sponseller CA, Waclawiw M, Alston-Smith B, Cooper-Arnold K, Klingman KL, Desvigne-Nickens P, Hoffmann U, Ribaudo HJ, Douglas PS; REPRIEVE Investigators. Rationale and design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Am Heart J. 2019 Jun;212:23-35. doi: 10.1016/j.ahj.2018.12.016. Epub 2019 Mar 4.
• Hoffmann U, Lu MT, Olalere D, Adami EC, Osborne MT, Ivanov A, Aluru JS, Lee S, Arifovic N, Overton ET, Fichtenbaum CJ, Aberg JA, Alston-Smith B, Klingman KL, Waclawiw M, Burdo TH, Williams KC, Zanni MV, Desvigne-Nickens P, Cooper-Arnold K, Fitch KV, Ribaudo H, Douglas PS, Grinspoon SK; REPRIEVE Investigators. Rationale and design of the Mechanistic Substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE): Effects of pitavastatin on coronary artery disease and inflammatory biomarkers. Am Heart J. 2019 Jun;212:1-12. doi: 10.1016/j.ahj.2019.02.011. Epub 2019 Mar 4.
• Grinspoon SK, Douglas PS, Hoffmann U, Ribaudo HJ. Leveraging a Landmark Trial of Primary Cardiovascular Disease Prevention in Human Immunodeficiency Virus: Introduction From the REPRIEVE Coprincipal Investigators. J Infect Dis. 2020 Jul 9;222(Suppl 1):S1-S7. doi: 10.1093/infdis/jiaa098.
• Fitch KV, Kileel EM, Looby SE, Zanni MV, Sanchez LR, Fichtenbaum CJ, Overton ET, Malvestutto C, Aberg JA, Klingman KL, Alston-Smith B, Lavelle J, Rancourt A, Badal-Faesen S, Cardoso SW, Avihingsanon A, Patil S, Sponseller CA, Melbourne K, Ribaudo HJ, Cooper-Arnold K, Desvigne-Nickens P, Hoffmann U, Douglas PS, Grinspoon SK; REPRIEVE Investigators. Successful recruitment of a multi-site international randomized placebo-controlled trial in people with HIV with attention to diversity of race and ethnicity: critical role of central coordination. HIV Res Clin Pract. 2020 Feb;21(1):11-23. doi: 10.1080/25787489.2020.1733794. Epub 2020 Mar 11.
• Overton ET, Kantor A, Fitch KV, Muntner P, Supparatpinyo K, Mosepele M, Mohapi L, Cardoso SW, Patil S, de Lacerda MVG, McComsey G, Aberg JA, Douglas PS, Grinspoon SK, Ribaudo H, Wyatt CM. An Evaluation of Baseline Kidney Function in the REPRIEVE Trial of Pitavastatin in Human Immunodeficiency Virus. J Infect Dis. 2020 Jul 9;222(Suppl 1):S41-S51. doi: 10.1093/infdis/jiaa222.
• Smeaton LM, Kileel EM, Grinsztejn B, Gardner EM, Starr K, Murry ML, Desvigne-Nickens P, Alston-Smith B, Waclawiw MA, Cooper-Arnold K, Madruga JV, Sangle S, Fitch KV, Zanni MV, Douglas PS, Ribaudo HJ, Grinspoon SK, Klingman KL. Characteristics of REPRIEVE Trial Participants Identifying Across the Transgender Spectrum. J Infect Dis. 2020 Jul 9;222(Suppl 1):S31-S40. doi: 10.1093/infdis/jiaa213.
• Zanni MV, Currier JS, Kantor A, Smeaton L, Rivard C, Taron J, Burdo TH, Badal-Faesen S, Lalloo UG, Pinto JA, Samaneka W, Valencia J, Klingman K, Allston-Smith B, Cooper-Arnold K, Desvigne-Nickens P, Lu MT, Fitch KV, Hoffman U, Grinspoon SK, Douglas PS, Looby SE. Correlates and Timing of Reproductive Aging Transitions in a Global Cohort of Midlife Women With Human Immunodeficiency Virus: Insights From the REPRIEVE Trial. J Infect Dis. 2020 Jul 9;222(Suppl 1):S20-S30. doi: 10.1093/infdis/jiaa214.
• Neilan TG, Nguyen KL, Zaha VG, Chew KW, Morrison L, Ntusi NAB, Toribio M, Awadalla M, Drobni ZD, Nelson MD, Burdo TH, Van Schalkwyk M, Sax PE, Skiest DJ, Tashima K, Landovitz RJ, Daar E, Wurcel AG, Robbins GK, Bolan RK, Fitch KV, Currier JS, Bloomfield GS, Desvigne-Nickens P, Douglas PS, Hoffmann U, Grinspoon SK, Ribaudo H, Dawson R, Goetz MB, Jain MK, Warner A, Szczepaniak LS, Zanni MV. Myocardial Steatosis Among Antiretroviral Therapy-Treated People With Human Immunodeficiency Virus Participating in the REPRIEVE Trial. J Infect Dis. 2020 Jul 9;222(Suppl 1):S63-S69. doi: 10.1093/infdis/jiaa245.
• Douglas PS, Umbleja T, Bloomfield GS, Fichtenbaum CJ, Zanni MV, Overton ET, Fitch KV, Kileel EM, Aberg JA, Currier J, Sponseller CA, Melbourne K, Avihingsanon A, Bustorff F, Estrada V, Ruxrungtham K, Saumoy M, Navar AM, Hoffmann U, Ribaudo HJ, Grinspoon S. Cardiovascular Risk and Health Among People With Human Immunodeficiency Virus (HIV) Eligible for Primary Prevention: Insights From the REPRIEVE Trial. Clin Infect Dis. 2021 Dec 6;73(11):2009-2022. doi: 10.1093/cid/ciab552.
• Hoffmann U, Lu MT, Foldyna B, Zanni MV, Karady J, Taron J, Zhai BK, Burdo T, Fitch KV, Kileel EM, Williams K, Fichtenbaum CJ, Overton ET, Malvestutto C, Aberg J, Currier J, Sponseller CA, Melbourne K, Floris-Moore M, Van Dam C, Keefer MC, Koletar SL, Douglas PS, Ribaudo H, Mayrhofer T, Grinspoon SK; REPRIEVE trial. Assessment of Coronary Artery Disease With Computed Tomography Angiography and Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for Primary Cardiovascular Prevention. JAMA Netw Open. 2021 Jun 1;4(6):e2114923. doi: 10.1001/jamanetworkopen.2021.14923.
• Kileel EM, Lo J, Malvestutto C, Fitch KV, Zanni MV, Fichtenbaum CJ, Overton ET, Okeke NL, Kumar P, Joao E, Aberg JA, Martinez E, Currier JS, Douglas PS, Ribaudo HJ, Grinspoon SK. Assessment of Obesity and Cardiometabolic Status by Integrase Inhibitor Use in REPRIEVE: A Propensity-Weighted Analysis of a Multinational Primary Cardiovascular Prevention Cohort of People With Human Immunodeficiency Virus. Open Forum Infect Dis. 2021 Nov 20;8(12):ofab537. doi: 10.1093/ofid/ofab537. eCollection 2021 Dec.
• Fulda ES, Fitch KV, Overton ET, Zanni MV, Aberg JA, Currier JS, Lu MT, Malvestutto C, Fichtenbaum CJ, Martinez E, Umbleja T, Douglas PS, Ribaudo HJ, Grinspoon SK. COVID-19 Vaccination Rates in a Global HIV Cohort. J Infect Dis. 2022 Feb 15;225(4):603-607. doi: 10.1093/infdis/jiab575.
• Bloomfield GS, Weir IR, Ribaudo HJ, Fitch KV, Fichtenbaum CJ, Moran LE, Bedimo R, de Filippi C, Morse CG, Piccini J, Zanni MV, Lu MT, Hoffmann U, Grinspoon SK, Douglas PS. Prevalence and Correlates of Electrocardiographic Abnormalities in Adults With HIV: Insights From the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). J Acquir Immune Defic Syndr. 2022 Mar 1;89(3):349-359. doi: 10.1097/QAI.0000000000002877.
• Erlandson KM, Fitch KV, McCallum SA, Ribaudo HJ, Overton ET, Zanni MV, Bloomfield GS, Brown TT, Fichtenbaum CJ, Bares S, Aberg JA, Douglas PS, Fulda ES, Santana-Bagur JL, Castro JG, Moran LE, Mave V, Supparatpinyo K, Ponatshego PL, Schechter M, Grinspoon SK. Geographical Differences in the Self-Reported Functional Impairment of People With Human Immunodeficiency Virus (HIV) and Associations With Cardiometabolic Risk. Clin Infect Dis. 2022 Sep 30;75(7):1154-1163. doi: 10.1093/cid/ciac098.
• Looby SE, Kantor A, Burdo TH, Currier JS, Fichtenbaum CJ, Overton ET, Aberg JA, Malvestutto CD, Bloomfield GS, Erlandson KM, Cespedes M, Kallas EG, Masia M, Thornton AC, Smith MD, Flynn JM, Kileel EM, Fulda E, Fitch KV, Lu MT, Douglas PS, Grinspoon SK, Ribaudo HJ, Zanni MV. Factors Associated With Systemic Immune Activation Indices in a Global Primary Cardiovascular Disease Prevention Cohort of People With Human Immunodeficiency Virus on Antiretroviral Therapy. Clin Infect Dis. 2022 Oct 12;75(8):1324-1333. doi: 10.1093/cid/ciac166.
• Overton ET, Weir IR, Zanni MV, Fischinger S, MacArthur RD, Aberg JA, Fitch KV, Frank M, Albrecht H, Goodenough E, Rhame FS, Fichtenbaum CJ, Bloomfield GS, Malvestutto C, Supparatpinyo K, McCallum S, Douglas PS, Alter G, Ribaudo H, Grinspoon SK. Asymptomatic SARS-CoV-2 Infection Is Common Among ART-Treated People With HIV. J Acquir Immune Defic Syndr. 2022 Aug 1;90(4):377-381. doi: 10.1097/QAI.0000000000003000.
• Fitch KV, McCallum SA, Erlandson KM, Overton ET, Zanni MV, Fichtenbaum C, Aberg JA, Fulda ES, Kileel EM, Moran LE, Bloomfield GS, Novak RM, Perez-Frontera S, Abrams-Downey A, Pierone G Jr, Kumarasamy N, Ruxrungtham K, Mngqibisa R, Douglas PS, Ribaudo HJ, Grinspoon SK. Diet in a global cohort of adults with HIV at low-to-moderate traditional cardiovascular disease risk. AIDS. 2022 Nov 15;36(14):1997-2003. doi: 10.1097/QAD.0000000000003344. Epub 2022 Jul 27.
• Kolossvary M, deFilippi C, Lu MT, Zanni MV, Fulda ES, Foldyna B, Ribaudo H, Mayrhofer T, Collier AC, Bloomfield GS, Fichtenbaum C, Overton ET, Aberg JA, Currier J, Fitch KV, Douglas PS, Grinspoon SK. Proteomic Signature of Subclinical Coronary Artery Disease in People With HIV: Analysis of the REPRIEVE Mechanistic Substudy. J Infect Dis. 2022 Nov 11;226(10):1809-1822. doi: 10.1093/infdis/jiac196.
• Zanni MV, Foldyna B, McCallum S, Burdo TH, Looby SE, Fitch KV, Fulda ES, Autissier P, Bloomfield GS, Malvestutto CD, Fichtenbaum CJ, Overton ET, Aberg JA, Erlandson KM, Campbell TB, Ellsworth GB, Sheth AN, Taiwo B, Currier JS, Hoffmann U, Lu MT, Douglas PS, Ribaudo HJ, Grinspoon SK. Sex Differences in Subclinical Atherosclerosis and Systemic Immune Activation/Inflammation Among People With Human Immunodeficiency Virus in the United States. Clin Infect Dis. 2023 Jan 13;76(2):323-334. doi: 10.1093/cid/ciac767.
• Schnittman SR, Lu MT, Mayrhofer T, Burdo TH, Fitch KV, McCallum S, Fulda ES, Zanni MV, Foldyna B, Malvestutto C, Fichtenbaum CJ, Aberg JA, Bloomfield GS, Overton ET, Currier J, Tebas P, Sha BE, Ribaudo HJ, Flynn JM, Douglas PS, Erlandson KM, Grinspoon SK. Cytomegalovirus Immunoglobulin G (IgG) Titer and Coronary Artery Disease in People With Human Immunodeficiency Virus (HIV). Clin Infect Dis. 2023 Feb 8;76(3):e613-e621. doi: 10.1093/cid/ciac662.
• Douglas PS, McCallum S, Lu MT, Umbleja T, Fitch KV, Foldyna B, Zanni MV, Fulda ES, Bloomfield GS, Fichtenbaum CJ, Overton ET, Aberg JA, Malvestutto CD, Burdo TH, Arduino RC, Ho KS, Yin MT, Ribaudo HJ, Grinspoon SK. Ideal cardiovascular health, biomarkers, and coronary artery disease in persons with HIV. AIDS. 2023 Mar 1;37(3):423-434. doi: 10.1097/QAD.0000000000003418. Epub 2022 Nov 18.
• Fulda ES, Fichtenbaum CJ, Kileel EM, Zanni MV, Aberg JA, Malvestutto C, Cardoso SW, Berzins B, Lira R, Harden R, Robbins G, Martinez M, Nieves SD, McCallum S, Cruz JL, Umbleja T, Sprenger H, Giguel F, Bone F, Wood K, Byroads M, Paradis K, Lu MT, Douglas PS, Ribaudo HJ, Grinspoon SK, Fitch KV; REPRIEVE Investigators. The importance of methods for site performance evaluation in REPRIEVE, a longitudinal, global, multicenter trial. Contemp Clin Trials. 2023 Jan;124:107035. doi: 10.1016/j.cct.2022.107035. Epub 2022 Nov 30.
• Schnittman SR, Jung W, Fitch KV, Zanni MV, McCallum S, Lee JS, Shin S, Davis BJ, Fulda ES, Diggs MR, Giguel F, Chinchay R, Sheth AN, Fichtenbaum CJ, Malvestutto C, Aberg JA, Currier J, Lauffenburger DA, Douglas PS, Ribaudo HJ, Alter G, Grinspoon SK. Effect of host factors and COVID-19 infection on the humoral immune repertoire in treated HIV. JCI Insight. 2023 Mar 8;8(5):e166848. doi: 10.1172/jci.insight.166848.
• Kileel EM, Malvestutto CD, Lo J, Fitch KV, Fichtenbaum CJ, Aberg JA, Zanni MV, Martinez E, Okeke NL, Kumar P, Joao E, Bares SH, Berrner D, Smieja M, Roa JC, McCallum S, Douglas PS, Ribaudo HJ, Grinspoon SK. Changes in Body Mass Index with Longer-term Integrase Inhibitor Use: A Longitudinal Analysis of Data from the Randomized Trial to Prevent Vascular Events in Human Immunodeficiency Virus (REPRIEVE). Clin Infect Dis. 2023 Jun 8;76(11):2010-2013. doi: 10.1093/cid/ciad107.
• Schnittman SR, Kitch DW, Swartz TH, Burdo TH, Fitch KV, McCallum S, Flynn JM, Fulda ES, Diggs MR, Stapleton JT, Casado JL, Taron J, Currier JS, Zanni MV, Malvestutto C, Fichtenbaum CJ, Aberg JA, Ribaudo HJ, Lu MT, Douglas PS, Grinspoon SK. Coronary Artery Plaque Composition and Severity Relate to the Inflammasome in People With Treated Human Immunodeficiency Virus. Open Forum Infect Dis. 2023 Mar 1;10(3):ofad106. doi: 10.1093/ofid/ofad106. eCollection 2023 Mar.
• Kolossvary M, deFilippi C, McCallum S, Fitch KV, Diggs MR, Fulda ES, Ribaudo HJ, Fichtenbaum CJ, Aberg JA, Malvestutto CD, Currier JS, Casado JL, Gutierrez F, Sereti I, Douglas PS, Zanni MV, Grinspoon SK. Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV. EBioMedicine. 2023 Apr;90:104538. doi: 10.1016/j.ebiom.2023.104538. Epub 2023 Mar 24.
• Foldyna B, Mayrhofer T, Zanni MV, Lyass A, Barve R, Karady J, McCallum S, Burdo TH, Fitch KV, Paradis K, Fulda ES, Diggs MR, Bloomfield GS, Malvestutto CD, Fichtenbaum CJ, Aberg JA, Currier JS, Ribaudo HJ, Hoffmann U, Lu MT, Douglas PS, Grinspoon SK. Pericoronary Adipose Tissue Density, Inflammation, and Subclinical Coronary Artery Disease Among People With HIV in the REPRIEVE Cohort. Clin Infect Dis. 2023 Dec 15;77(12):1676-1686. doi: 10.1093/cid/ciad419.
• Grinspoon SK, Fitch KV, Zanni MV, Fichtenbaum CJ, Umbleja T, Aberg JA, Overton ET, Malvestutto CD, Bloomfield GS, Currier JS, Martinez E, Roa JC, Diggs MR, Fulda ES, Paradis K, Wiviott SD, Foldyna B, Looby SE, Desvigne-Nickens P, Alston-Smith B, Leon-Cruz J, McCallum S, Hoffmann U, Lu MT, Ribaudo HJ, Douglas PS; REPRIEVE Investigators. Pitavastatin to Prevent Cardiovascular Disease in HIV Infection. N Engl J Med. 2023 Aug 24;389(8):687-699. doi: 10.1056/NEJMoa2304146. Epub 2023 Jul 23.
• Lake JE, Taron J, Ribaudo HJ, Leon-Cruz J, Utay NS, Swaminathan S, Fitch KV, Kileel EM, Paradis K, Fulda ES, Ho KS, Luetkemeyer AF, Johnston CD, Zanni MV, Douglas PS, Grinspoon SK, Lu MT, Fichtenbaum CJ; REPRIEVE Trial Investigators. Hepatic steatosis and nonalcoholic fatty liver disease are common and associated with cardiometabolic risk in a primary prevention cohort of people with HIV. AIDS. 2023 Nov 15;37(14):2149-2159. doi: 10.1097/QAD.0000000000003671. Epub 2023 Jul 27.
• Schnittman SR, Kolossvary M, Beck-Engeser G, Fitch KV, Ambayec GC, Nance RM, Zanni MV, Diggs M, Chan F, McCallum S, Toribio M, Bamford L, Fichtenbaum CJ, Eron JJ, Jacobson JM, Mayer KH, Malvestutto C, Bloomfield GS, Moore RD, Umbleja T, Saag MS, Aberg JA, Currier JS, Delaney JAC, Martin JN, Lu MT, Douglas PS, Ribaudo HJ, Crane HM, Hunt PW, Grinspoon SK. Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus. Open Forum Infect Dis. 2023 Sep 8;10(10):ofad467. doi: 10.1093/ofid/ofad467. eCollection 2023 Oct.
• Bhattacharya R, Uddin MM, Patel AP, Niroula A, Finneran P, Bernardo R, Fitch KV, Lu MT, Bloomfield GS, Malvestutto C, Aberg JA, Fichtenbaum CJ, Hornsby W, Ribaudo HJ, Libby P, Ebert BL, Zanni MV, Douglas PS, Grinspoon SK, Natarajan P. Risk factors for clonal hematopoiesis of indeterminate potential in people with HIV: a report from the REPRIEVE trial. Blood Adv. 2024 Feb 27;8(4):959-967. doi: 10.1182/bloodadvances.2023011324.
• Zou RS, Ruan Y, Truong B, Bhattacharya R, Lu MT, Karady J, Bernardo R, Finneran P, Hornsby W, Fitch KV, Ribaudo HJ, Zanni MV, Douglas PS, Grinspoon SK, Patel AP, Natarajan P. Polygenic Scores and Preclinical Cardiovascular Disease in Individuals With HIV: Insights From the REPRIEVE Trial. J Am Heart Assoc. 2024 Apr 2;13(7):e033413. doi: 10.1161/JAHA.123.033413. Epub 2024 Mar 27.
• Grinspoon SK, Ribaudo HJ, Douglas PS. Trial Update of Pitavastatin to Prevent Cardiovascular Events in HIV Infection. N Engl J Med. 2024 May 2;390(17):1626-1628. doi: 10.1056/NEJMc2400870. No abstract available.
• Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB Sr, Gibbons R, Greenland P, Lackland DT, Levy D, O'Donnell CJ, Robinson JG, Schwartz JS, Shero ST, Smith SC Jr, Sorlie P, Stone NJ, Wilson PWF. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2935-2959. doi: 10.1016/j.jacc.2013.11.005. Epub 2013 Nov 12. No abstract available.
• Fichtenbaum CJ, Ribaudo HJ, Leon-Cruz J, Overton ET, Zanni MV, Malvestutto CD, Aberg JA, Kileel EM, Fitch KV, Van Schalkwyk M, Kumarasamy N, Martinez E, Santos BR, Joseph Y, Lo J, Siminski S, Melbourne K, Sponseller CA, Desvigne-Nickens P, Bloomfield GS, Currier JS, Hoffmann U, Douglas PS, Grinspoon SK; REPRIEVE Investigators. Patterns of Antiretroviral Therapy Use and Immunologic Profiles at Enrollment in the REPRIEVE Trial. J Infect Dis. 2020 Jul 9;222(Suppl 1):S8-S19. doi: 10.1093/infdis/jiaa259.
• Lu MT, Ribaudo H, Foldyna B, Zanni MV, Mayrhofer T, Karady J, Taron J, Fitch KV, McCallum S, Burdo TH, Paradis K, Hedgire SS, Meyersohn NM, DeFilippi C, Malvestutto CD, Sturniolo A, Diggs M, Siminski S, Bloomfield GS, Alston-Smith B, Desvigne-Nickens P, Overton ET, Currier JS, Aberg JA, Fichtenbaum CJ, Hoffmann U, Douglas PS, Grinspoon SK; REPRIEVE Trial Writing Group. Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers in HIV: Mechanistic Substudy of the REPRIEVE Randomized Clinical Trial. JAMA Cardiol. 2024 Apr 1;9(4):323-334. doi: 10.1001/jamacardio.2023.5661.
• Corley MJ, Watanabe M, Pang APS, Dwaraka VB, Smith R, Samaneka W, Henn S, Munsiff S, Saumoy M, McCallum S, Fitch KV, Chu SM, Diggs MR, Aberg JA, Malvestutto CD, Fichtenbaum CJ, Currier JS, Zanni MV, Douglas PS, Lu MT, Landay AL, Erlandson KM, Ribaudo HJ, Grinspoon SK. Effect of Pitavastatin on Epigenetic Aging Biomarkers in People With HIV: Pilot Substudy of the REPRIEVE Trial. Clin Infect Dis. 2025 Jun 18:ciaf247. doi: 10.1093/cid/ciaf247. Online ahead of print.
• Fichtenbaum CJ, Malvestutto CD, Watanabe MG, Davies Smith E, Ribaudo HJ, McCallum S, Fitch KV, Currier JS, Diggs MR, Chu SM, Aberg JA, Lu MT, Valencia J, Gomez-Ayerbe C, Brar I, Valdez Madruga J, Bloomfield GS, Douglas PS, Zanni MV, Grinspoon SK; REPRIEVE Investigators. Effects of antiretrovirals on major adverse cardiovascular events in the REPRIEVE trial: a longitudinal cohort analysis. Lancet HIV. 2025 Jul;12(7):e496-e505. doi: 10.1016/S2352-3018(25)00043-8. Epub 2025 Jun 4.
• Lu MT, Ribaudo HJ, McCallum S, Zanni MV, deFilippi C, Taron J, Karady J, Foldyna B, Paradis K, Chu SM, Diggs MR, Burdo TH, Currier JS, Bloomfield GS, Fichtenbaum CJ, Malvestutto CD, Aberg JA, Mayrhofer T, Douglas PS, Grinspoon SK; REPRIEVE Investigators. Coronary Plaque, Inflammation, Subclinical Myocardial Injury, and Major Adverse Cardiovascular Events in the REPRIEVE Substudy. JACC Adv. 2025 Jun;4(6 Pt 1):101781. doi: 10.1016/j.jacadv.2025.101781. Epub 2025 May 14.
• Davies Smith E, Malvestutto C, Ribaudo HJ, Fichtenbaum CJ, Aberg JA, Watanabe M, Bloomfield GS, Currier JS, Chu SM, Fitch KV, Diggs MR, Bedimo R, Valencia J, Gomez-Ayerbe C, Brar I, Madruga JV, Lu MT, Douglas PS, Zanni MV, Grinspoon SK. Cardiovascular Hazards of Abacavir- Versus Tenofovir-Containing Antiretroviral Therapies: Insights From an Analysis of the REPRIEVE Trial Cohort. Open Forum Infect Dis. 2025 Mar 21;12(4):ofaf177. doi: 10.1093/ofid/ofaf177. eCollection 2025 Apr.
• Diggs MR, Umbleja T, McCallum S, Zanni MV, Chu SM, Fitch KV, Bloomfield GS, Currier JS, Martinez E, Castle PE, Awwad A, Jain MK, Bedimo R, Hendricks B, Narrea J, Estrada V, Pinto J, Aberg JA, Malvestutto CD, Fichtenbaum CJ, Lu MT, Ribaudo HJ, Douglas PS, Grinspoon SK. Statin effects on the incidence of major non-cardiovascular disease events among a global cohort of people with HIV: a randomised controlled trial. Lancet HIV. 2025 Apr;12(4):e261-e272. doi: 10.1016/S2352-3018(24)00345-X.
• Grinspoon SK, Zanni MV, Triant VA, Kantor A, Umbleja T, Diggs MR, Chu SM, Fitch KV, Currier JS, Bloomfield GS, Casado JL, de la Pena M, Fantry LE, Gardner E, Aberg JA, Malvestutto CD, Fichtenbaum CJ, Lu MT, Ribaudo HJ, Douglas PS. 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. Lancet HIV. 2025 Feb;12(2):e118-e129. doi: 10.1016/S2352-3018(24)00276-5. Epub 2025 Jan 17.
• Kolossvary M, Schnittman SR, Zanni MV, Fitch KV, Fichtenbaum CJ, Aberg JA, Bloomfield GS, Malvestutto CD, Currier J, Diggs MR, deFilippi C, Eckard AR, Curran A, Centinbas M, Sadreyev R, Foldyna B, Mayrhofer T, Karady J, Taron J, McCallum S, Lu MT, Ribaudo HJ, Douglas PS, Grinspoon SK. Pitavastatin, Procollagen Pathways, and Plaque Stabilization in Patients With HIV: A Secondary Analysis of the REPRIEVE Randomized Clinical Trial. JAMA Cardiol. 2025 Mar 1;10(3):254-264. doi: 10.1001/jamacardio.2024.4115.
• Zanni MV, Umbleja T, Fichtenbaum CJ, Fitch KV, McCallum S, Aberg JA, Overton ET, Malvestutto CD, Bloomfield GS, Currier JS, Schnittman SR, Erlandson KM, Diggs MR, Foldyna B, Martinez E, Somboonwit C, Wang GP, Mushatt D, Connick E, Lu MT, Douglas PS, Ribaudo HJ, Grinspoon SK. Effects of Pitavastatin on COVID-19 Incidence and Seriousness Among a Global Cohort of People With HIV. Open Forum Infect Dis. 2024 Oct 10;11(10):ofae574. doi: 10.1093/ofid/ofae574. eCollection 2024 Oct.
• Fitch KV, Zanni MV, Manne-Goehler J, Diggs MR, Gattu AK, Currier JS, Bloomfield GS, Hsiao CB, Gupta SK, Aberg JA, Malvestutto CD, Fichtenbaum CJ, Lu MT, Douglas PS, Ribaudo HJ, Grinspoon SK. Diabetes Risk Factors in People With HIV Receiving Pitavastatin Versus Placebo for Cardiovascular Disease Prevention : A Randomized Trial. Ann Intern Med. 2024 Nov;177(11):1449-1461. doi: 10.7326/ANNALS-24-00944. Epub 2024 Oct 8.
• deFilippi C, McCallum S, Zanni MV, Fitch KV, Diggs MR, Bloomfield GS, Fichtenbaum CJ, Aberg JA, Malvestutto CD, Pinto-Martinez A, Stapleton A, Duggan J, Robbins GK, Taron J, Karady J, Foldyna B, Lu MT, Ribaudo HJ, Douglas PS, Grinspoon SK. Association of Cardiac Troponin T With Coronary Atherosclerosis in Asymptomatic Primary Prevention People With HIV. JACC Adv. 2024 Aug 16;3(9):101206. doi: 10.1016/j.jacadv.2024.101206. eCollection 2024 Sep.
• Erlandson KM, Umbleja T, Ribaudo HJ, Schrack JA, Overton ET, Fichtenbaum CJ, Fitch KV, Roa JC, Diggs MR, Wood K, Zanni MV, Bloomfield GS, Malvestutto C, Aberg JA, Rodriguez-Barradas MC, Morones RG, Breaux K, Douglas PS, Grinspoon SK, Brown TT. Pitavastatin Is Well-Tolerated With no Detrimental Effects on Physical Function. Clin Infect Dis. 2025 Feb 24;80(2):425-433. doi: 10.1093/cid/ciae422.
• Abidi MZ, Umbleja T, Overton ET, Burdo T, Flynn JM, Lu MT, Taron J, Schnittman SR, Fitch KV, Zanni MV, Fichtenbaum CJ, Malvestutto C, Aberg JA, Fulda ES, Eckard AR, Manne-Goehler J, Tuan JJ, Ribaudo HJ, Douglas PS, Grinspoon SK, Brown TT, Erlandson KM. Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV. J Acquir Immune Defic Syndr. 2024 Apr 15;95(5):470-478. doi: 10.1097/QAI.0000000000003377.
• Erlandson KM, Umbleja T, Lu MT, Taron J, Ribaudo HJ, Overton ET, Presti RM, Haas DW, Sax PE, Yin MT, Zhai BK, Louis R, Upadhyay N, Eslami P, Douglas PS, Zanni MV, Fitch KV, Fulda ES, Fichtenbaum CJ, Malvestutto CD, Grinspoon SK, Brown TT. Associations of Muscle Density and Area With Coronary Artery Plaque and Physical Function. J Acquir Immune Defic Syndr. 2023 Oct 1;94(2):174-184. doi: 10.1097/QAI.0000000000003244.

Helpful Links

• REPRIEVE Trial Website
• Clinical Safety Data Management: Definitions and Standards for Expedited Reporting E2A
• Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2015
• Primary Completion (Actual): August 21, 2023
• Study Completion (Actual): August 21, 2023

Study Registration Dates

• First Submitted: January 16, 2015
• First Submitted That Met QC Criteria: January 16, 2015
• First Posted (Estimated): January 22, 2015

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Cholesterol; HIV; Cardiovascular Disease; COVID-19; Statin; Myocardial Infarction; Computerized Tomography
• Additional Relevant MeSH Terms: Vascular Diseases; Pathologic Processes; Heart Diseases; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Infarction; Necrosis; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Myocardial Ischemia; Ischemia; Pathological Conditions, Signs and Symptoms; COVID-19; Cardiovascular Diseases; Inflammation; Myocardial Infarction; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; pitavastatin
• Other Study ID Numbers: A5332; 11960 (Other Identifier: DAIDS-ES Registry Number); 1U01HL123339-01 (U.S. NIH Grant/Contract); 1U01HL123336-01 (U.S. NIH Grant/Contract); EU5332 (Other Identifier: Massachusetts General Hospital)