The effect of statin use on vascular inflammatory biomarkers in people living with HIV: A living systematic review of randomized controlled trials

Objective: To evaluate the effect of statin therapy on biomarkers of vascular inflammation in people living with HIV (PLWH). Methods: We conducted a living systematic review of randomized controlled trials (RCTs). We searched Scopus, PubMed, Cochrane Library, and Scilit up to April 4, 2025, with a predefined plan for ongoing evidence surveillance and updating. Nine RCTs involving 1721 participants were included. Data were extracted on changes in key biomarkers, including interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), soluble CD14 (sCD14), soluble CD163 (sCD163), oxidized LDL (oxLDL), and lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). The Cochrane Risk of Bias (RoB 2) tool was used for quality assessment. This review is not intended to be retired from the living mode at this stage. Results: Statin therapy significantly reduced key biomarkers of monocyte activation and vascular inflammation, particularly IL-6 and sCD14, with effects being most consistent and pronounced with pitavastatin. Pitavastatin also demonstrated greater efficacy in reducing oxLDL and Lp-PLA 2 compared to other statins. Reductions in hs-CRP were inconsistent across studies. A critical finding was that treatment duration was a major modifier of effect, with interventions lasting ≥12 months yielding substantially greater anti-inflammatory benefits. The mechanistic profile suggests statins specifically target the LPS-sCD14 pathway of innate immune activation, which is highly relevant to HIV pathogenesis. Conclusions: Pitavastatin emerges as the most effective statin for reducing vascular inflammation in PLWH, offering a targeted strategy to mitigate cardiovascular disease risk in this population. These findings, derived from the current iteration of a living systematic review, support the use of long-term pitavastatin therapy for PLWH with evidence of residual inflammation and highlight the need for its inclusion in future clinical guidelines as new evidence continues to emerge.