Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults
The study is funded by the National Heart, Lung, and Blood Institute, with additional infrastructure support provided by the National Institute of Allergy and Infectious Diseases. 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).
Randomized Trial to Prevent Vascular Events in HIV - REPRIEVE (A5332)
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.
HIV Infections Cardiovascular Diseases HIV Cardiovascular Disease Myocardial Infarction Inflammation Statin Computerized Tomography Cholesterol Pitavastatin
You can join if…
Open to people ages 40-75
- HIV-1 infected individuals
- Combination antiretroviral therapy (ART) for at least 180 days prior to study entry
CD4+ cell count greater than 100 cells/mm3
- 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/1.73m2 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
- Men and women 40 to 75 years of age
- Ability and willingness of participant or legal representative to provide written informed consent
You CAN'T join if...
- 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
- 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
- UCSD Antiviral Research Center CRS
San Diego California 92103 United States
- Eisenhower Health Center at Rimrock CRS
Palm Springs California 92264 United States