Statin Therapy for Cardiovascular Disease Prevention in People Living with Human Immunodeficiency Virus: A Systematic Review of Efficacy, Safety, and Clinical Challenges

Abstract

Background: Advances in antiretroviral therapy (ART) have prolonged survival among people living with
human immunodeficiency virus (PLWH), but shifted morbidity toward non-communicable diseases, particularly
cardiovascular disease (CVD), with PLWH experiencing a twofold higher myocardial infarction risk and increased
heart failure and sudden death risk. This systematic review aimed to provide a comprehensive overview of the
epidemiology, pathophysiology, and management of CVD in PLWH, with a particular focus on statin therapy.
Methods: In April 2024, MEDLINE/PubMed, Scopus, Google Scholar, ClinicalTrials.gov, and CENTRAL were
searched for peer-reviewed randomized clinical trials and observational studies in adults (≥18 years) comparing
statins with placebo or non-statin lipid-lowering therapy and reporting cardiovascular events, lipid outcomes,
adverse events, and ART interactions; two reviewers independently screened, extracted data, and narratively
synthesized the findings. Results: Statins lower low-density lipoprotein cholesterol (approximately 15–35% in
human immunodeficiency virus cohorts), increase high-density lipoprotein cholesterol, and improve surrogate
vascular measures and plaque characteristics, including non-calcified/high-risk plaque features. They also exhibit
immunomodulatory effects, reducing vascular inflammation and markers such as soluble cluster of differentiation 14,
lipoprotein-associated phospholipase A2, interferon-gamma-inducible protein 10, and T-cell/monocyte activation,
although their effects on systemic inflammation and CD4 count are inconsistent. Clinically, pitavastatin reduced
serious cardiovascular events by 35% compared to placebo in a trial of >7,700 PLWH aged ≥40 years on ART,
supporting its broader preventive use. Conclusion:
Overall, statins, particularly pitavastatin, are a
cornerstone for CVD risk reduction in PLWH;
however, individualized prescribing, safety
monitoring, and outcome research remain essential