In a landmark advancement poised to reshape cardiovascular care in people living with HIV (PWH), a specialized panel convened by the U.S. Department of Health and Human Services (HHS) has issued new statin therapy recommendations aimed at mitigating the heightened risk of atherosclerotic cardiovascular disease (ASCVD) in this vulnerable population. These guidelines emerge in the wake of compelling findings from the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) study, a robust global phase 3 randomized controlled trial that compared the efficacy of pitavastatin, a moderate-intensity statin, to placebo in preventing cardiovascular events among PWH aged 40 to 75 years who fall into a low to intermediate ten-year ASCVD risk category.
The impetus for these recommendations lies in the growing recognition that PWH experience accelerated aging-related comorbidities, notably ASCVD, with rates surpassing those of the general population. Chronic immune activation and inflammation, residual viral replication, and antiretroviral therapy (ART) side effects compound traditional risk factors, necessitating nuanced cardiovascular risk stratification and prevention strategies tailored specifically to PWH. REPRIEVE’s rigorous investigation enrolled thousands of individuals across multiple continents, assessing pitavastatin’s capacity to attenuate major adverse cardiovascular events (MACE), which encompasses myocardial infarction, stroke, and cardiovascular death.
The trial’s striking outcome—a 36% relative reduction in MACE among the pitavastatin arm compared to placebo—underscores the potential of statin therapy as a cornerstone of primary prevention in the HIV-infected demographic. Statins’ pleiotropic effects, including anti-inflammatory properties and endothelial function stabilization, are believed to underlie these benefits, complementing their lipid-lowering actions. Such findings have informed the HHS Antiretroviral Treatment Guidelines Panel to endorse moderate-intensity statin use, specifically citing pitavastatin at 4 mg daily, atorvastatin at 20 mg daily, or rosuvastatin at 10 mg daily as viable options.
Crucially, the panel delineates initiation thresholds standardized to the 10-year ASCVD risk score, advocating statin therapy in PWH exhibiting a calculated risk of 5% or greater. For those with risk scores below this threshold, the recommendation is more nuanced—favoring statin consideration informed by individualized clinician–patient discussions highlighting HIV-specific variables that could heighten ASCVD susceptibility beyond conventional metrics. Such factors include chronic inflammation biomarkers, ART history, and non-traditional risk enhancers intrinsic to HIV pathobiology. In younger patients under 40, the panel advises tailored decision-making predicated on familial history and cumulative risk exposures, acknowledging gaps in existing data.
The recommendations emphasize moderate-intensity statins partly because of their safety profile and minimal pharmacokinetic interactions with antiretroviral regimens. Pitavastatin, distinctively metabolized via pathways less involved in cytochrome P450 enzyme systems, offers a reduced risk of drug-drug interactions, making it especially suitable for PWH who often receive complex polypharmacy. Despite these advances, the panel underscores the urgent need for continued research dissecting absolute cardiovascular risk and exploring nonischemic cardiac manifestations common in HIV, such as cardiomyopathies and arrhythmias, which remain poorly characterized.
These clinical guidelines represent a vital paradigm shift given the historical underrepresentation of PWH in cardiovascular prevention trials and the prior absence of HIV-focused primary prevention protocols. They advocate for an integrative approach merging cardiology and HIV specialty care to optimize statin utilization and mitigate cardiovascular morbidity. Physicians are encouraged to incorporate comprehensive risk assessments that transcend traditional lipid measurements, incorporating inflammatory markers and potential subclinical atherosclerosis imaging that may reveal early vascular disease in PWH.
As PWH live longer due to advances in ART, managing comorbid conditions like ASCVD becomes paramount to preserving quality of life. This guideline update arrives at a critical juncture, aligning with a broader shift in HIV care that prioritizes aging-related comorbidity management. It also illuminates unresolved questions about statins’ broader impact in HIV beyond lipid modulation, including potential antiviral activity and immunomodulatory effects that may influence HIV reservoir dynamics and systemic inflammation.
The panel’s work was a collaborative effort involving the American College of Cardiology, the American Heart Association, and the HIV Medicine Association, bringing multifaceted expertise to balance efficacy, safety, and patient-centered care considerations. The development process incorporated rigorous evidence appraisal and deliberations of trial data quality, benefit-harm balance, and implementation feasibility in diverse healthcare settings.
In tandem with guideline dissemination, educational initiatives are crucial to enhance clinician awareness regarding the distinct cardiovascular risk profile in PWH and the modern nuances of statin therapy. Stigma, healthcare access disparities, and comorbid substance use remain barriers necessitating multidisciplinary efforts to ensure equitable statin uptake. Moreover, patient engagement in shared decision-making fosters adherence and empowers PWH to participate actively in their cardiovascular health management.
Future investigative directions recommended by the panel include long-term observational cohort studies and mechanistic trials elucidating statins’ effects on inflammation, immune activation, and viral persistence. Additionally, head-to-head comparisons of different statin agents in the HIV population could further refine therapeutic choices. Integration of advanced cardiovascular imaging modalities and biomarker panels may enhance personalized risk stratification, enabling precision prevention strategies.
This evolving guidance marks a pivotal step toward closing a critical gap in HIV care, positioning statin therapy as a foundational preventive measure against cardiovascular disease, which remains a leading cause of morbidity and mortality in the HIV community. As the body of evidence consolidates, the routine incorporation of statins into primary prevention paradigms for PWH promises to advance health outcomes and sustain the gains achieved through antiretroviral therapy.
Subject of Research: People
Article Title: Statin Therapy as Primary Prevention for Persons with HIV: Recommendations from the U.S. HHS Antiretroviral Treatment Guidelines Panel
News Publication Date: 27-May-2025
Web References: http://dx.doi.org/10.7326/ANNALS-24-03564
Keywords: Statins, Human immunodeficiency virus, Antiretrovirals
