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

Abstract

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 1 721 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 A₂ (Lp-PLA₂). 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-PLA₂ 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.

Keywords

Living systematic review / Human immunodeficiency virus / Cardiovascular disease / Statin / Inflammatory biomarkers

Conflict of interest statement

The authors declare that there is no conflict of interests.

Funding

The authors received no extramural funding for the study.

Authors’ contributions

M.H. conceptualized the study, performed the literature search, extracted the data, and drafted the manuscript. M.A.N. contributed to data collection, literature screening, and manuscript editing. K.F.J. supervised the study design and critically revised the manuscript. D.D. contributed to data interpretation and methodological evaluation. M.S. contributed to quality assessment and final manuscript revision. All authors reviewed and approved the final version of the manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Edited by Zhang Q, Lei Y, Pan Y

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