NCT02344290: REPRIEVE

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

Completed Phase 3 Results posted Last updated 4 September 2025

What this trial tests

Phase 3 trial testing Pitavastatin in HIV in 7,769 participants. Completed in 21 August 2023.

Timeline

26 March 2015

Primary endpoint
21 August 2023

21 August 2023

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	7,769
Start date	26 March 2015
Primary completion	21 August 2023
Estimated completion	21 August 2023
Sites	137 locations across Zimbabwe, Haiti, South Africa, Uganda, Peru, Botswana, Canada, Puerto Rico

Drugs / interventions tested

• Pitavastatin (PITAVASTATIN) — full drug profile →
• Placebo

Conditions studied

• HIV — all drugs for HIV →
• Cardiovascular Diseases — all drugs for Cardiovascular Diseases →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 40 to 75, any sex, with HIV or Cardiovascular Diseases. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Incidence Rate of Major Adverse Cardiovascular Event (MACE) Primary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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, strat

Group	Value	95% CI
Pitavastatin	4.95	4.07 – 6.03
Placebo	7.77	6.64 – 9.08

Incidence Rate of Cardiac Ischemia or Myocardial Infarction Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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 init

Group	Value	95% CI
Pitavastatin	1.48	1.03 – 2.11
Placebo	2.65	2.03 – 3.46

Incidence Rate of Cerebrovascular Event (Stroke or TIA) Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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 initiati

Group	Value	95% CI
Pitavastatin	1.53	1.07 – 2.17
Placebo	2.46	1.86 – 3.24

Incidence Rate of Peripheral Arterial Ischemia Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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 sta

Group	Value	95% CI
Pitavastatin	0.10	0.02 – 0.39
Placebo	0.15	0.05 – 0.45

Incidence Rate of Death From CV Causes Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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

Group	Value	95% CI
Pitavastatin	0.69	0.41 – 1.16
Placebo	0.98	0.63 – 1.51

Incidence Rate of Death From CV or Undetermined Causes Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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 car

Group	Value	95% CI
Pitavastatin	1.72	1.23 – 2.39
Placebo	2.54	1.94 – 3.33

Incidence Rate of Cardiac Catheterization or Revascularization Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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, includi

Group	Value	95% CI
Pitavastatin	1.08	0.71 – 1.64
Placebo	1.77	1.27 – 2.45

Incidence Rate of Carotid or Cerebrovascular Revascularization Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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 i

Group	Value	95% CI
Pitavastatin	0	NA – NA
Placebo	0	NA – NA

Incidence Rate of Peripheral Arterial Revascularization Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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 initiati

Group	Value	95% CI
Pitavastatin	0	NA – NA
Placebo	0.29	0.13 – 0.65

Incidence Rate of MACE or Death Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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).

Group	Value	95% CI
Pitavastatin	9.31	8.07 – 10.75
Placebo	12.02	10.60 – 13.63

Incidence Rate of Death (All-cause) Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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).

Group	Value	95% CI
Pitavastatin	6.18	5.19 – 7.36
Placebo	6.99	5.93 – 8.23

Incidence Rate of Non-CV Clinical Diagnoses Secondary · From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).

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 proportiona

Group	Value	95% CI
Pitavastatin	9.17	7.93 – 10.59
Placebo	9.90	8.61 – 11.38

Adverse events — posted to ClinicalTrials.gov

Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pitavastatin

Serious: 750/3888 (19%)

Deaths: 126/3888

Placebo

Serious: 755/3881 (19%)

Deaths: 143/3881

Serious adverse events (415 terms)

Reaction	System	Pitavastatin	Placebo
Lower respiratory tract and lung infections	Infections and infestations	—	—
Limb fractures and dislocations	Injury, poisoning and procedural complications	—	—
Abdominal and gastrointestinal infections	Infections and infestations	—	—
Bacterial infections NEC	Infections and infestations	—	—
Suicidal and self-injurious behaviour	Psychiatric disorders	—	—
Bronchospasm and obstruction	Respiratory, thoracic and mediastinal disorders	—	—
Renal failure and impairment	Renal and urinary disorders	—	—
Pain and discomfort NEC	General disorders	—	—
Urinary tract infections	Infections and infestations	—	—
Pulmonary thrombotic and embolic conditions	Respiratory, thoracic and mediastinal disorders	—	—
Sepsis, bacteraemia, viraemia and fungaemia NEC	Infections and infestations	—	—
Cholecystitis and cholelithiasis	Hepatobiliary disorders	—	—
Anaemias NEC	Blood and lymphatic system disorders	—	—
Infections NEC	Infections and infestations	—	—
Disturbances in consciousness NEC	Nervous system disorders	—	—
Non-site specific injuries NEC	Injury, poisoning and procedural complications	—	—
Seizures and seizure disorders NEC	Nervous system disorders	—	—
Tuberculous infections	Infections and infestations	—	—
Cataract conditions	Eye disorders	—	—
Breathing abnormalities	Respiratory, thoracic and mediastinal disorders	—	—
Acute and chronic pancreatitis	Gastrointestinal disorders	—	—
Non-site specific gastrointestinal haemorrhages	Gastrointestinal disorders	—	—
Influenza viral infections	Infections and infestations	—	—
Diabetes mellitus (incl subtypes)	Metabolism and nutrition disorders	—	—
Musculoskeletal and connective tissue pain and discomfort	Musculoskeletal and connective tissue disorders	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	Pitavastatin	Placebo
Diabetes mellitus (incl subtypes)	Metabolism and nutrition disorders	—	—
Renal function analyses	Investigations	—	—
Muscle pains	Musculoskeletal and connective tissue disorders	—	—
General nutritional disorders NEC	Metabolism and nutrition disorders	—	—
Physical examination procedures and organ system status	Investigations	—	—
Vascular hypertensive disorders NEC	Vascular disorders	—	—
Musculoskeletal and connective tissue pain and discomfort	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: Lower respiratory tract and lung infections, Limb fractures and dislocations, Abdominal and gastrointestinal infections, Bacterial infections NEC, Suicidal and self-injurious behaviour, Bronchospasm and obstruction, Renal failure and impairment, Pain and discomfort NEC.

Data from ClinicalTrials.gov NCT02344290 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV: A Scientific Statement From the American Heart Association.
   Feinstein MJ, Hsue PY, Benjamin LA, Bloomfield GS, et al · · 2019 · cited 478× · PMID 31154814 · DOI 10.1161/cir.0000000000000695
2. Pitavastatin to Prevent Cardiovascular Disease in HIV Infection.
   Grinspoon SK, Fitch KV, Zanni MV, Fichtenbaum CJ, et al · · 2023 · cited 350× · PMID 37486775 · DOI 10.1056/nejmoa2304146
3. Immunologic Biomarkers, Morbidity, and Mortality in Treated HIV Infection.
   Hunt PW, Lee SA, Siedner MJ. · · 2016 · cited 216× · PMID 27625430 · DOI 10.1093/infdis/jiw275
4. HIV and cardiovascular disease.
   So-Armah K, Benjamin LA, Bloomfield GS, Feinstein MJ, et al · · 2020 · cited 204× · PMID 32243826 · DOI 10.1016/s2352-3018(20)30036-9
5. Inflammation, immune activation, and cardiovascular disease in HIV.
   Nou E, Lo J, Grinspoon SK. · · 2016 · cited 181× · PMID 27058351 · DOI 10.1097/qad.0000000000001109
6. Rationale and design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE).
   Grinspoon SK, Fitch KV, Overton ET, Fichtenbaum CJ, et al · · 2019 · cited 131× · PMID 30928825 · DOI 10.1016/j.ahj.2018.12.016
7. Metabolic Complications and Glucose Metabolism in HIV Infection: A Review of the Evidence.
   Willig AL, Overton ET. · · 2016 · cited 116× · PMID 27541600 · DOI 10.1007/s11904-016-0330-z
8. Lipid Abnormalities and Inflammation in HIV Inflection.
   Funderburg NT, Mehta NN. · · 2016 · cited 107× · PMID 27245605 · DOI 10.1007/s11904-016-0321-0