John Kastner, PharmD, Goodrich Pharmacy
Background
The incredible advances in antiretroviral therapy and viral suppression have led to longer lives for people with HIV (PWH). In fact, the estimated mortality gap for those with HIV compared to those without is now 10 years or less. With this remarkable achievement however, a new problem emerges for patients and their providers- an increased risk for atherosclerotic cardiovascular disease (ASCVD). Compared to those without, patients with HIV have roughly a twofold higher risk for developing ASCVD, and the age at which they are diagnosed is nearly a decade younger. This higher risk can be attributed to both traditional factors such as obesity and smoking, the prevalence of which tends to be higher in PWH, but also due to HIV-specific factors such as ongoing systemic inflammation, prior immune depletion, and/or toxicity from some antiretroviral medications. Furthermore, structural barriers and health disparities in screening and treating ASCVD risk factors (hypertension, diabetes, etc.) likely contribute to an overall higher risk of ASCVD among PWH. Despite these risks, there were no recommendations for statin use for the primary prevention of ASCVD specifically in people with HIV, prior to 2024. The 2018 ACC/AHA guidelines of the management of blood cholesterol identify HIV as a “risk enhancer” that can be used to guide decisions for primary prevention in patients at a borderline or intermediate risk of ASCVD (5-20%), but without strong randomized clinical trial data, the guidelines remained vague.
Evidence:
In June 2025, the Annals of Internal Medicine published a synopsis of recommendations from the U.S. Department of HHS Antiretroviral Treatment Guidelines Panel and discussed how they supplement the 2018 AHA/ACC guidelines for the general population. The expert panel reviewed data from the REPRIEVE trial, other studies evaluating the use of statins in PWH, and the AHA/ACC/multisociety cholesterol guidelines to devise their recommendations.
REPRIEVE (The Randomized Trial to Prevent Vascular Events in HIV) was the first ever large scale, randomized clinical trial to study the primary prevention of ASCVD among people living with HIV. It enrolled participants between 2015 and 2019, and the study concluded in 2023. Over 7,500 people with HIV were enrolled at over 100 clinical sites. The main objective of REPRIEVE was to test whether a daily dose of pitavastatin reduced the occurrence of major adverse cardiac events (MACE), defined as a composite of CVD death; myocardial infarction (MI); hospitalization for unstable angina; stroke; transient ischemic attack; peripheral arterial ischemia; revascularization of coronary, carotid, or peripheral artery; or death of undetermined cause. REPRIEVE found that compared to placebo, pitavastatin was associated with a 36% reduction in MACE (hazard ratio, 0.64 [95% CI, 0.48 to 0.84]).
Discussion
Statins have long been thought to have an especially beneficial impact for PWH over other primary prevention strategies not only due to their well documented reduction in ASCVD events, but also because of their effects on inflammatory pathways. The overall findings from REPRIEVE, combined with the observation that equations based on traditional risk factors underestimate ASCVD risk among PWH, led to the Panel’s decision to recommend the use of at least moderate-intensity statin therapy as primary prevention among PWH aged 40 to 75 years with low to intermediate 10-year ASCVD risk (<20%).
The Panel issued a strong recommendation for initiating statin therapy among individuals with a risk score greater than 5%, and a weaker recommendation for individuals with a lower risk (<5%). There are additional HIV-related factors that clinicians should consider when deciding whether to initiate a statin in lower risk individuals (<5%). These include: history of prolonged HIV viremia (whether due to delayed ART initiation, nonadherence, or treatment failure), low current or nadir CD4 count (<0.350 × 109 cells/L), lipodystrophy or lipoatrophy, metabolic syndrome, fatty liver disease, and co-infection with hepatitis C, longer duration of HIV infection, and exposure to older ARV drugs with cardiometabolic toxicity such as zidovudine, protease inhibitors, or abacavir.
While pitavastatin specifically was chosen in the REPRIEVE trial due to its lower potential for drug interactions, the Panel’s recommendations also include atorvastatin and rosuvastatin as potential treatment options. However, it should be noted that these two drugs have drug–drug interactions with ritonavir- and cobicistat-boosted antiretroviral medications.
The Annals of Internal Medicine synopsis goes on to discuss other important issues related ASCVD risk/treatment in PWH. Most people with HIV in the world live in sub-Saharan Africa and risk prediction tools have not typically been validated in these countries. This creates uncertainty about the risks and benefits of statins in these populations. It also discusses continued efforts to improve CVD risk estimating calculations across all populations, including PWH, which could include additional inflammatory biomarkers. Finally, it discusses the need for further research into the use of other lipid modifying agents such as ezetimibe, PCSK9 inhibitors, and bempedoic acid.
Clinical Impact
The ARV Guidelines Panel’s decision to issue a strong recommendation for initiating statin therapy in people with HIV with a 10-year ASCVD risk score of 5% or higher will likely increase utilization of these medications in this population. For practitioners who may not be aware that HIV was listed as an ASCVD risk enhancer in the 2018 ACC/AHA guidelines, or for those who didn’t know by how much that specific risk enhancer should favor choosing a statin, these new recommendations provide more clarity. For patients with HIV who fall into the “borderline risk” (5% to <7.5%) category, the 2018 guidelines only gave a Class IIb recommendation for statin initiation. These updates strengthen that recommendation. For patients with a risk score below 5%, the previous guidelines emphasized lifestyle changes over statin therapy, but based on the new recommendations, a patient–clinician risk discussion should be had that considers additional HIV-related factors that can increase ASCVD risk, and then possibly initiating a statin. Of note, these recommendations only apply to individuals between the ages of 40-75. REPRIEVE did not study anyone outside this age group so there is insufficient data to make a strong recommendation. Optimizing lifestyle factors (including smoking cessation, diet, and exercise) remains paramount regardless of statin use.
Published on November 17th, 2025.
References
Qaseem A, Barry MJ, Lin JS, et al. Screening for breast cancer in average-risk women: A guidance statement from the American College of Physicians. Ann Intern Med. Published July 30, 2024. Accessed July 30, 2025. https://www.acpjournals.org/doi/10.7326/ANNALS-24-03564
Panel on Antiretroviral Guidelines for Adults and Adolescents. Statin therapy in people with HIV. Clinicalinfo HIV.gov. Published June 3, 2024. Accessed July 30, 2025. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/statin-therapy-adult-adolescent-arv.pdf