Classical monocyte transcriptomes reveal significant anti-inflammatory statin effect in women with chronic HIV

Area of Science:

• Immunology
• Cardiology
• Infectious Diseases

Background:

• Chronic HIV infection, even when virally suppressed, is linked to persistent inflammation and increased cardiovascular disease (CVD) risk.
• Classical monocytes (CMs) in people living with HIV (PLWH) remain activated, producing pro-inflammatory and pro-thrombotic factors that drive atherosclerosis.

Purpose of the Study:

• To investigate transcriptomic changes in circulating CMs in PLWH with and without subclinical CVD (sCVD).
• To assess the impact of statin use on CM inflammatory profiles in PLWH.

Main Methods:

• Analysis of peripheral blood mononuclear cells from the Women's Interagency HIV Study.
• Flow-sorting of CMs followed by deep mRNA sequencing (n=92).
• Comparison of transcriptomic data between HIV-positive (HIV+) and HIV-negative (HIV-) participants, with and without sCVD.

Main Results:

• CMs from HIV+ participants exhibited elevated levels of IL-6, IL-1β, and IL-12β, similar to transcripts found in sCVD+ participants.
• In PLWH with sCVD, statin use was associated with reduced pro-inflammatory gene expression, comparable to healthy individuals.
• Statin non-users maintained an elevated inflammatory profile and increased cytokine production.

Conclusions:

• Statin therapy may offer cardiovascular benefits to women living with HIV, even without overt CVD.
• Findings suggest statins can modulate the inflammatory pathways driven by CMs in PLWH.