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Statin reduces the risk of cardiovascular disease in people living with HIV

REPRIEVE trial demonstrated that daily pitavastatin reduced the risk of cardiovascular disease in people living with HIV by 35%.
About REPRIEVE Trial

REPRIEVE is the first-ever randomized clinical trial to determine whether statin use prevents atherosclerotic cardiovascular disease events in persons with HIV infection who are at low-to-moderate risk for cardiovascular events.1

The investigators used pitavastatin calcium as the statin in this study because it does not interact with the drugs that are used in antiretroviral therapy.

This information is intended for Healthcare Providers. Please note the limitation of use statement in both the Livalo (pitavastatin calcium) and Zypitamag (pitavastatin magnesium) Package Inserts. The effect of Pitavastatin on cardiovascular morbidity and mortality has not been determined.

HIV, Cardiovascular Disease, and Statins

People living with HIV infection are living longer and longer thanks to advancements in medications to manage HIV infection. As a result, this patient population is now living long enough to experience non-AIDS-defining illnesses and, notably, cardiovascular disease.

People with HIV are at a much greater risk for cardiovascular disease than the general population.

The risk of myocardial infarction in people with HIV is 1.5–2.0 times higher, and dyslipidemia has been reported in up to 80%. Possible mechanisms for this include a combination of chronic inflammation and dysregulation of the immune system.

Mortality from cardiovascular disease has increased substantially from 1999 to 2013 for people living with HIV while this number has consistently gone down for the general population.2

Mortality from cardiovascular disease in people with HIV
Adapted from Figure 3 in Feinstein MJ, et al. Am J Cardiol. 2016;115(12):1760-6.

Statin Use In People With HIV

Treating dyslipidemia has historically been challenging for this patient population given the increased potential for drug interactions due to competing cytochrome P450 (CYP450) metabolism with statins and antiretroviral therapies. These interactions can lead to issues with efficacy and statin tolerability.

There is also a lack of data in this patient population and lack of guideline recommendations, leaving prescribers without great guidance on how to manage this patient population.

Data analyzed from the National Ambulatory Medical Care Survey from 2006 to 2013 identified that physicians generally underused guideline-recommend cardiovascular care in people living with HIV.3

Medical Therapy in Patients with CV Risk Factors
Adapted from Figure 1 of Ladapo JA et al. J Am Heart Assoc. 2017;6:e007107.

This data may explain higher rates of adverse cardiovascular events among patients with HIV in the U.S., given that they are being untreated compared to the general patient population.

Improved Access to Pitavastatin through Marley Drug

Pitavastatin is available under the brand name Livalo (pitavastatin calcium) and Zypitamag (pitavastatin magnesium). The FDA considers these medications to be bioequivalent.

Marley Drug pharmacy offers Zypitamag (Pitavastatin) for $1.15/day or $34.50/month. The first 30 days are free for new patients to allow them to try the medication and ensure they can tolerate it.

Zypitamag is also available on certain AIDS Drug Assistance Program (ADAP) state formularies. Find more information here.

* Conditions apply. Visit for more information.
† Livalo® pricing based on Average Wholesale Price.

Statin Drug Interactions

Most statins are processed by the CYP450 family of enzymes, which can lead to drug interactions when paired with antiretroviral therapy.

Two statins, Pitavastatin and pravastatin, are only minimally processed by the CYP450 pathway and are reasonable treatment options for those living with HIV who have high cholesterol.

Statin Metabolism

How pitavastatin and pravastatin are processed by our bodies

The principal route of pitavastatin metabolism is glucuronidation via liver uridine 5'-diphosphate glucuronosyltransferase (UGT) with subsequent formation of pitavastatin lactone. There is only minimal metabolism by the cytochrome P450 system. Pitavastatin is marginally metabolized by CYP2C9 and to a lesser extent by CYP2C8. Pravastatin is processed by CYP3A4 (part of CYP450), but unlike other statins it’s not extensively metabolized by this enzyme. Instead, it’s mostly excreted unchanged in the bile. Because CYP450 isn’t significantly involved in pravastatin’s metabolism, pravastatin also has a decreased risk of drug interactions.

Due to these interactions, and previous randomized trials, which demonstrated pitavastatin was clinically superior to pravastatin in people living with HIV (see data below), pitavastatin was the statin of choice for the REPRIEVE trial.

Pitavastatin Clinically Superior to Pravastatin in those with HIV4

The INTREPID trial was a randomized, double-blind, active-controlled, phase 4 trial which recruited adults aged 18–70 years with controlled HIV who were on antiretroviral therapy for at least six months and dyslipidemia.

Patients were randomized to receive pitavastatin 4mg (n=126) or pravastatin 40mg (n=126) once daily for 12 weeks, followed by a 40-week safety extension.

At 12 weeks, LDL-cholesterol was reduced by 31.1% with pitavastatin and 20.9% with pravastatin.

Pitavastatin vs Pravastatin in People Living with HIV
Mean percent changes at week 12
4 mg
40 mg
ApoB -26% -19%
Triglycerides -3% -4%
HDL-C +5% +6%
hsCRP -12% 0%

This study excluded patients being treated with darunavir, or who had homozygous familial hypercholesterolemia, or any condition causing secondary dyslipidemia, or a history of statin intolerance, diabetes, or coronary artery disease.

Both treatments have a neutral effect on glucose metabolism parameters.

Pitavastatin is as Accessible as a Generic Statin Through Marley Drug

Your patients can access Zypitamag (Pitavastatin) throughout the pharmacy without needing insurance. That means:

  • No prior authorizations
  • No step therapy
  • No insurance hassles

One consistent price. Just $1.15/day.

Send prescriptions to Marley Drug, and your patients will receive the first 30 days for Zypitamag free.

REPRIEVE Trial Design

The REPRIEVE trial randomized 7769 participants who were living with HIV infection on stable antiretroviral therapy (ART) at low-to-moderate risk of cardiovascular disease to pitavastatin 4 mg or placebo (for up to 8 years).

The purpose of the REPRIEVE trial was to determine whether statin use prevents atherosclerotic cardiovascular disease events in persons with HIV infection who are at low-to-moderate risk for cardiovascular events.

Asymptomatic people with HIV on ART with 10-year ASCVD risk ≤15%
Placebo vs. Pitavastatin 4 mg/day
Primary Endpoint: MACE (CV Death, MI, Unstable Angina, TIA/Stroke, Revascularization, PAD)
Secondary Endpoints:
  • Individual components of primary endpoint and all cause mortality
  • Predictors of statin effects
  • Inflammatory, immunological, metabolic markers
  • Statin safety and non-AIDS comorbidities, infections, cancer

    For the primary endpoint, MACE was defined as cardiovascular (CV) death, myocardial infarction (MI), hospitalization for unstable angina, stroke, transient ischemic attack (TIA), peripheral arterial ischemia (PAD), revascularization, or death from an undetermined cause.

    The study excluded anyone who took a statin in the last 90 days, and those with known atherosclerotic cardiovascular disease.

    REPRIEVE Trial Results

    Daily pitavastatin reduced the risk of cardiovascular disease in people living with HIV by 35%.

    The pitavastatin group had a significantly lower incidence of major adverse cardiovascular events than those in the placebo group, with a hazard reduction of 35% over a median of 5.1 years of follow-up.

    Pitavastatin lowers indidence of cardiovascular events in people with HIV

    Treatment with pitavastatin was consistent across major subgroups, including men and women, and across different global regions. In addition, there were no differences in groups based on CD4 count levels or duration of ART therapy.

    Safety Events

    The incidence of nonfatal serious adverse events was similar in both groups. There was a higher rate of diabetes mellitus in the pitavastatin group. There was no apparent treatment effect on glucose levels.

    A higher number of muscle-related symptoms were reported in the pitavastatin group. However, a very small portion of patients discontinued their medication (1.1% in the pitavastatin group vs. 0.5% in the placebo group).

    Event Pitavastatin (N=3888) Placebo (N=3881) Indidence Rate Ratio
    (95% CI)
    No. With Event Incidence Rate
    (No/100 person-yr)
    No. With Event Incidence Rate
    (No/100 person-yr)
    Nonfatal serious advers event 695 4.16 694 1.01 1.01
    Diabetes mellitus 206 1.13 155 0.84 1.35
    Myalgia, or myopathy of grade ≥3 or treatment limiting 91 0.49 53 0.28 1.74
    Rhabdomyolsis of grade ≥ 3 or treatment limiting 3 0.02 4 0.02 0.75
    Alanine aminotransferase elevation of grade ≥3 11 0.06 8 0.04 1.38
    Any adverse event 1304 8.88 1256 8.37 1.06

    Key Takeaways of REPRIEVE Trial

    • People living with HIV have elevated risks of cardiovascular disease
    • Despite HIV being considered a risk equivalent, no prior trial has assessed a primary prevention strategy for this group who would not typically be recommended for statin therapy
    • Taking a daily statin can lower the risk by more than one-third. Among persons living with HIV 40-75 years of age, on ART, with low-to-moderate risk, and normal range LDL, treatment with pitavastatin is effective and prevents major adverse cardiovascular events.
    • Considerations should be given to expanding treatment guidelines in this regard 
    Get the First 30-days of Pitavastatin FREE through Marley Drug

    We offer patients the first 30 days of Zypitamag (pitavastatin) free with a valid prescription.

    Medications are shipped via USPS First Class Mail and arrive in 2-3 business days.

    Please note the limitation of use statement in both the Livalo (pitavastatin calcium) and Zypitamag (pitavastatin magnesium) Package Inserts. The effect of pitavastatin on cardiovascular morbidity and mortality has not been determined. 


    1 Grinspoon SK et al. Pitavastatin to Prevent Cardiovascular Disease in HIV Infection. The New England Journal of Medicine. 2023; DOI: 10.1056/NEJMoa2304146.
    2 Feinstein MJ et al. Patterns of Cardiovascular Mortality for HIV-Infected Adults in the United States: 1999 to 2013. American Journal of Cardiology. 2016;117(2):214-220.
    3 Ladapo JA et al. Disparities in the Quality of Cardiovascular Care Between HIV-Infected Versus HIV-Uninfected Adults in the United States: A Cross-Sectional Study. Journal of the American Heart Association. 2017;6(11):e007107.
    4 Aberg JA et a. Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised, double-blind, superiority trial. Lancet HIV. 2017;4:e284-94.