Long-Term Cardiovascular Benefits and Neurocognitive Risks of Statin Therapy in People Living With HIV: A Global Real-World Cohort Study

Background People living with HIV (PLWH) are at risk for atherosclerotic cardiovascular disease (ASCVD) and neurocognitive impairment. Statins are recommended for primary and secondary prevention of ASCVD; however, their potential impact on cognitive function among PLWH is uncertain. We evaluated the association between statin use and incident cognitive impairment in a large, real-world cohort of adults with HIV. Methods Using the TriNetX Global Collaborative Network, we identified adults (≥ 18 years) with HIV and comorbidities and stratified them into two cohorts based on statin use versus no statin use. Individuals with pre-existing dementia, substance use disorders, major psychiatric illness, or use of CNS-active antipsychotics were excluded. Outcomes included cognitive impairment, major adverse cardiovascular events (MACE: myocardial infarction, stroke, or death), all-cause mortality, hospital utilization, myopathy, and transaminitis. Propensity score matching (1:1) balanced demographics, comorbidities, medications, and laboratory values. Cox proportional-hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs); p < 0.05 was considered statistically significant. Results After matching, 38,292 individuals were analyzed (mean age 54 ± 13 years; 24% female, 76% White). Cognitive impairment occurred in 9.1% of statin users versus 6.6% of non-users (HR 1.20, 95% CI:1.11–1.29; p < 0.001). All-cause mortality was lower among statin users (5.3% vs 8.0%; HR 0.58, 95% CI: 0.53–0.63; p < 0.001). MACE was lower among statin users (7.9% vs 8.7%; HR 0.79, 95% CI: 0.74–0.85; p < 0.001). Statin use was associated with higher risks of myopathy (2.9% vs 2.0%; HR 1.25, 95% CI: 1.09–1.43; p = 0.001), transaminitis (12.4% vs 9.2%; HR 1.20, 95% CI:1.12–1.28; p < 0.001), and hospital utilization (2.2% vs 1.7%; HR 1.12, 95% CI:1.05–1.20; p < 0.001). Appendicitis (negative control) was similar between groups (0.2% each; HR 0.86, 95% CI:0.53–1.38; p = 0.52). Conclusions In this large, real-world cohort of PLWH, statin use was associated with lower all-cause mortality and MACE but a modestly increased risk of cognitive impairment (11–29%) over ten years. Statin users had greater comorbidity burden, highlighting the need to balance cardiovascular benefits against potential neurocognitive risks.