The Utilization of Inclisiran for the Optimization of Lipid Management in People Living with HIV: A Clinical Case Series and Comprehensive Review

Background and Clinical Significance: People with HIV (PWH) experience an elevated risk of atherosclerotic cardiovascular disease (ASCVD), driven by chronic immune activation, metabolic toxicities of antiretroviral therapy (ART), and traditional risk factors. Achieving target low-density lipoprotein cholesterol (LDL-C) levels is frequently impeded by adherence barriers, pharmacokinetic drug interactions, or muscle-related symptoms. Inclisiran is a hepatocyte-targeted small interfering RNA that halts proprotein convertase subtilisin/kexin type 9 synthesis, providing a long-acting therapeutic alternative. Case Presentation: We present two PWH with severe hypercholesterolemia and elevated cardiovascular risk on stable ART. Case 1 describes a 54-year-old male with a history of myocardial infarction presenting with persistent, refractory hypercholesterolemia on rosuvastatin and ezetimibe (baseline LDL-C 142 mg/dL). Case 2 describes a 58-year-old male with verified statin intolerance and inadequate response to ezetimibe (baseline LDL-C 194 mg/dL). Following subcutaneous inclisiran administration at Day 1 and Day 90, Case 1 achieved an 80.2% LDL-C reduction to 28 mg/dL at Month 6, and Case 2 achieved a 54.6% reduction to 88 mg/dL at Month 6 as monotherapy. Both patients tolerated therapy well, with stable CD4+ counts and sustained virological suppression. Conclusions: These cases illustrate that inclisiran can effectively lower LDL-C levels across primary and secondary prevention settings in PWH facing oral therapy limitations or statin intolerance. Provider-administered dosing every 6 months overcomes adherence challenges, supporting the inclusion of PWH in broader clinical pathways pending ongoing cardiovascular outcome trials.