Beyond Lipid Lowering: A Narrative Review and Expert Perspective on Precision Cardiovascular Prevention in People with HIV After REPRIEVE

Abstract

The spectrum of diseases in individuals with human immunodeficiency virus (HIV) receiving successful antiretroviral therapy has evolved over time. In the past, they developed opportunistic infections and malignancies, whereas today, cardiovascular disease is among the most common causes of illness and premature death. Traditional risk factors for atherosclerosis (hypertension, hyperlipidemia, smoking, diabetes, family history of heart disease) are more prevalent in people with HIV than in the general population. However, it is well established that HIV itself causes increased immune activation, chronic inflammation, vascular dysfunction, and a cluster of metabolic abnormalities that contribute to a faster-than-usual rate of biological aging and a higher risk of developing atherosclerosis, a risk not fully captured by current risk models. In the REPRIEVE study, treatment with pitavastatin was shown to reduce the rate of first cardiovascular events among individuals with HIV receiving antiretroviral therapy. Importantly, the beneficial effects of statins on atherosclerosis likely extend beyond lowering cholesterol to include effects on vascular function and on immune and metabolic systems altered by HIV. Even among individuals on statins, a considerable risk of cardiovascular disease remains. Here, We provide a narrative review of current evidence and an expert perspective on emerging approaches to residual cardiovascular risk after REPRIEVE. We review the current understanding of atherosclerosis pathogenesis in individuals with HIV, focusing on recent findings from the REPRIEVE trial. We outline current approaches to improving cardiovascular risk assessment across clinical, biological, and computational levels. We also examine a growing number of therapeutic options that address residual inflammation and atherogenic metabolic disturbance in individuals with HIV on long-term, effective antiretroviral therapy. Significantly, after REPRIEVE, we must move from prescribing statins to all individuals with HIV toward more individualized cardiovascular disease prevention strategies, integrating clinical information, a variety of biomarkers, imaging studies, and even molecular information to generate optimal individualized cardiovascular disease prevention regimens that reflect the complexity of this outcome in naturally diverse individuals.