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

The REPRIEVE trial consists of two parallel identical protocols:

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

Study Overview

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

Detailed Description

Currently, there are few strategies to prevent CVD in HIV-infected people, 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 people infected with HIV. The purpose of this study is to evaluate the use of pitavastatin to reduce the risk of CVD in adults infected with HIV who are on ART.

This study will enroll adults infected with HIV who are on any ART regimen (ART is not provided by the study) for at least 6 months before study entry considered low-to-moderate risk using the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline thresholds for recommended statin initiation. Total study duration will be approximately 96 months from the time the first participant is enrolled.

Participants will be randomly assigned to receive 4 mg of pitavastatin or placebo once a day for the entire time they are enrolled in the study. Study visits will occur at study entry (Day 0) and Months 1 and 4. Starting at Month 4, study visits will occur every 4 months for the rest of the study. Depending on when participants enroll, they will be in the study for a total of 3 to 8 years. Study visits will include 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).

Some participants will have the option of enrolling in a substudy (Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers: Mechanistic Substudy of REPRIEVE [A5333s]). The substudy will evaluate the effect of pitavastatin on the progression of non-calcified coronary atherosclerotic plaque (NCP) and inflammatory biomarkers in adults infected with HIV. Participants in the substudy will attend study visits at study entry and Months 4 and 24. The visits will include questionnaires and assessments, a blood collection, and a coronary computed tomography angiography (CCTA). NOTE: The Mechanistic Substudy of REPRIEVE (A5333s) closed to accrual on 02/06/18.

Participants enrolled in REPRIEVE from select study sites, including international sites, through December, 2017, are included in the REPRIEVE Kidney Function Objectives Cohort to evaluate the effects of pitavastatin on parameters of kidney function in the setting of HIV infection. The analyses will also include an assessment of high risk groups and mechanisms driving kidney function decline in the setting of HIV infection.

Women and men enrolled in REPRIEVE after February, 2016 are included in an observational cohort (REPRIEVE Women's Objectives Cohort) facilitating assessment of sex-specific mechanisms of CVD risk and risk reduction among adults with HIV. This effort also includes 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 risk, we will evaluate interrelated but independent key topics including epidemiology, host factors, and protective strategies. Starting from April 2020, COVID-19 assessment is completed at each study visit, and blood is collected for COVID-19 biomarkers.

• 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
  • Sao Paulo, Brazil, 01246-900
    • Instituto de Infectologia Emilio Ribas CRS
  • Sao 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 De Janeiro
    • Nova Iguacu, Rio De Janeiro, Brazil, 26030-380
      • HGNI HIV Family Care Clinic - HHFCC CRS
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao CRS
  • São Paulo
    • Sao 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
    • Quebec City, 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
  • San Juan, 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)
  • Kwa Zulu Natal
    • Durban, Kwa Zulu Natal, South Africa, 4052
      • Durban International Clinical Research Site CRS
  • Western Cape Province
    • Cape Town, Western Cape Province, South Africa, 7700
      • University of Cape Town Lung Institute (UCTLI) CRS
    • Tygerberg, Western Cape Province, 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 Clinico 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, 90035
      • UCLA CARE Center CRS
    • Los Angeles, California, United States, 90033-1079
      • University of Southern California CRS
    • 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
    • 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, District of Columbia, United States, 20005
      • Whitman-Walker Health CRS
    • Washington, District of Columbia, United States, 20007
      • Georgetown University CRS (GU CRS)
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, PC CRS
    • Washington, 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
      • Rush University CRS
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS
    • Chicago, Illinois, United States, 60612
      • UIC Project WISH 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, 02114
      • Massachusetts General Hospital CRS (MGH CRS)
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center CRS
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center 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
    • Saint 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
    • Bronx, New York, United States, 10468
      • James J Peters VA Medical Center CRS
    • New York, New York, United States, 10032-3732
      • Columbia P&S CRS
    • New York, New York, United States, 10065
      • Weill Cornell Uptown CRS
    • New York, New York, United States, 10003
      • Mount Sinai Beth Israel CRS
    • New York, New York, United States, 10010
      • VA New York Harbor Healthcare System (NYHHS), NY Campus 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, 10029
      • Infectious Disease Clinical and Translational Research Center (CTRC) CRS
    • Rochester, New York, United States, 14642
      • University of Rochester Adult HIV Therapeutic Strategies Network 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, 19104
      • Penn Therapeutics, CRS
    • 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
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh CRS
    • Pittsburgh, Pennsylvania, United States, 15212
      • Positive Health Clinic 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
      • Palmetto Health Clinical Trial Department 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
      • Houston AIDS Research Team CRS
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VAMC REPRIEVE 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:

• HIV-1 infected individuals
• 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 a:

  • Fasting low-density lipoprotein (LDL) cholesterol as follows: If ASCVD risk score is less than 7.5%, LDL cholesterol must be less than 190 mg/dL. If ASCVD risk score is greater than or equal to 7.5% and less than or equal to 10%, LDL must be less than 160 mg/dL. If ASCVD risk score is greater than 10% and less than or equal to 15%, LDL must be less than 130 mg/dL. NOTE: If LDL is less than 70 mg/dL, participant is eligible regardless of 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 be 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 if LDL is 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.

  • NOTE: Exceptions:

    • Successfully treated non-melanomatous skin cancer
    • 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. NOTE: Use of oral prednisone less than or equal to 10 mg/day or equivalent dosage is allowed.
• 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 will receive pitavastatin once a day for the entire time they are enrolled in the study.	Drug: Pitavastatin; One tablet (4 mg) taken once daily, orally with or without food
Placebo Comparator: Placebo; Participants will receive placebo for pitavastatin once a day for the entire time they are enrolled in the study.	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
Time to the first event of a composite of major cardiovascular events	Includes atherosclerotic or other CVD death, nonfatal myocardial infarction, unstable angina hospitalization, coronary, carotid or peripheral arterial revascularization, nonfatal stroke or transient ischemic attack (TIA), peripheral arterial ischemia	Measured through participants' final study visit, at approximately Month 36 to 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to death (all-cause mortality)	Time to death (all-cause mortality)	Measured through participants' final study visit, at approximately Month 36 to 96
Time to death (all-cause mortality) and/or major adverse cardiovascular events (MACE)	Time to death (all-cause mortality) and/or major adverse cardiovascular events (MACE)	Measured through participants' final study visit, at approximately Month 36 to 96
Time to any (composite) or each (individual) of the following clinical diagnoses (including recurrent diagnoses as appropriate)	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); initiation of dialysis or renal transplantation; cirrhosis, or hepatic decompensation requiring hospitalization.	Measured through participants' final study visit, at approximately Month 36 to 96
Calculated fasting low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) cholesterol level	Change from baseline expressed as absolute change and as a percentage of baseline. For participants with triglycerides greater than 400 mg/dL and less than 500 mg/dL, direct LDL will be determined and used in the statistical analysis.	Measured through participants' final study visit, at approximately Month 36 to 96
Time to any of the following adverse events (including recurrent events as appropriate)	Serious adverse event as defined by International Conference on Harmonisation (ICH) criteria, incident diabetes mellitus (DM), grade 3 or 4 ALT, or grade 3 or 4 myopathy.	Measured through participants' final study visit, at approximately Month 36 to 96
Incidence of COVID-19	COVID-19 is defined as COVID-19 clinical diagnosis or positive test.	Measured from 2020 to participants' final study visit, approximately for 3 years
Incidence of serious COVID-19	Serious COVID-19 is defined as COVID-19 related hospitalization or death.	Measured from 2020 to participants' final study visit, approximately for 3 years
For substudy: volume of NCP at study entry and change in NCP over 2 years	Expressed as absolute change and as a percentage of baseline.	Measured through Year 2
For substudy: evidence of non-calcified coronary atherosclerotic plaque (NCP)	For substudy: evidence of non-calcified coronary atherosclerotic plaque (NCP)	Measured through Year 2
For substudy: progression of NCP	Participants with evidence of NCP at entry: any progression/increase in NCP volume; participants without evidence of NCP at entry, incident NCP.	Measured through Year 2
For substudy: number of high risk plaque features	Low Hounsfield Unit attenuation by CT assessment; positive remodeling.	Measured through Year 2
For substudy: changes in inflammatory markers	Expressed as change in CRP, Lp-PLA2, sCD163	Measured through Year 2
Time to the first of each individual component of the primary endpoint	Includes atherosclerotic or other CVD death, nonfatal myocardial infarction, unstable angina hospitalization, coronary, carotid or peripheral arterial revascularization, nonfatal stroke or transient ischemic attack (TIA), peripheral arterial ischemia	Measured through participants' final study visit, at approximately Month 36 to 96

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

• 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.
• 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.
• 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.
• 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.
• 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.
• 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. Erratum In: J Infect Dis. 2021 Feb 3;223(2):352.
• 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.
• 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.

Helpful Links

• REPRIEVE Trial Website

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 (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Cholesterol; HIV; Cardiovascular Disease; COVID-19; Statin; Myocardial Infarction; Computerized Tomography
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; 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)