Updated Guidelines for Statin Therapy in Patients With HIV

In February, the Department of Health and Human Services Guidelines Panel for the Use of Antiretroviral Agents in Adults and Adolescents with HIV collaborated with the HIV Medicine Association and representatives from the American College of Cardiology (ACC) and the American Heart Association (AHA) to develop recommendations for patients with HIV regarding statin use. The recommendations were endorsed by these organizations following the publication of the REPRIEVE trial.¹

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The REPRIEVE trial, which stands for Randomized Trial to Prevent Vascular Events in HIV, was based on the strategy to test for heart disease prevention among individuals living with HIV.² This study addresses the burden of heart disease in patients living with HIV and impacts on the care and treatment of these individuals.

Previous studies have shown that individuals living with HIV are at higher risk for heart disease than individuals without HIV. The REPRIEVE trial was the first large-scale randomized clinical research study to demonstrate that pitavastatin was associated with a 35% reduction in major adverse cardiovascular events over a median follow-up duration of 5 years.²

Guideline Recommendations for Individuals With HIV

For individuals aged 40 to 75 years with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk between 5% and <20%, the panel recommended moderate intensity statin therapy. This approach includes pitavastatin 4 mg daily, atorvastatin 20 mg daily, or rosuvastatin 10 mg daily. If the 10-year ASCVD risk estimates are below 5%, the panel recommends considering other ASCVD risk factors regardless of HIV presence before deciding whether to initiate statin therapy.¹

For patients younger than 40 years with low ASCVD risk (5%-<20%), lifestyle modifications are recommended, and data are insufficient to determine whether statin therapy will be beneficial in individuals with HIV for primary prevention of ASCVD.¹

For individuals with a high (>20%) 10-year ASCVD risk estimate who are aged 40 to 75 years with HIV, the panel recommendations are similar to the general population and recommend initiating high-intensity statin therapy. Similarly, for individuals with HIV aged 20 to 75 years with low-density lipoprotein (LDL) levels > 190 mg/dL, the panel recommends initiating high-intensity statin therapy.¹

Finally, for individuals aged 40 to 75 years with HIV and diabetes mellitus, the panel recommends initiating moderate intensity statin therapy. Clinicians should also evaluate other risk factors that may warrant consideration of high-intensity statin therapy.¹

The REPRIEVE Trial

The REPRIEVE study was phase-3 randomized clinical control trial which included 7769 individuals with HIV with a low to moderate risk of cardiovascular disease who were receiving stable antiretroviral therapy. Participants were assigned 1:1 to receive oral pitavastatin 4 mg per day or placebo. Pitavastatin was chosen for the study due to its minimal interactions with antiretroviral therapy and ability to lower cholesterol levels.²

The primary outcome was occurrence of major adverse cardiovascular event (MACE), which comprised of cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, or death from an undetermined cause. A few key secondary outcomes included LDL, non–high-density lipoprotein (HDL) levels, and safety events (incident diabetes mellitus, liver injury, or musculoskeletal side effects).²

The median duration of follow-up was 5.1 years and a total of 6452 participants remained, with 74.8% in the treatment group and 71.0% in the placebo group. The trial was completed early for efficacy after a median follow-up of 5.1 years.²

In the primary outcome, the incidence of MACE was 4.81 per 1000 person-years in the pitavastatin group and 7.32 per 1000 person-years in the placebo group (HR, 0.65; 95% CI: 0.48 to 0.90; p=0.002).2 For the secondary outcome, occurrence of non-fatal serious events was similar between groups. In the treatment group, incidence of diabetes mellitus and grade >3 myalgia, muscle weakness, or myopathy was more likely to occur.²

The LDL levels were similar at trial initiation. The reduction of LDL levels in the pitavastatin group decreased from a median of 107 mg/dL to 74 mg/dL. In the placebo group, the LDL levels decreased from a median of 106 mg/dL to 105 mg/dL.²

Overall, individuals with HIV infection who received pitavastatin had a lower risk of MACE than those who received placebo for the median duration of 5.1 years, with a hazard reduction of 35%.²

References

1. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. What’s New in the Guidelines. Feburary 27, 2024. ClinicalInfo.HIV.org.

2. Grinspoon SK, Fitch KV, Zanni MV, et al. Pitavastatin to Prevent Cardiovascular Disease in HIV Infection. N Engl J Med. 2023;389(8):687-699. doi:10.1056/NEJMoa2304146