Differential Plasma Protein Regulation and Statin Effects in Human Immunodeficiency Virus (HIV)-Infected and...

Area of Science:

• Proteomics
• Cardiovascular Medicine
• Immunology

Background:

• People with human immunodeficiency virus (PWH) have higher risks of atherosclerotic cardiovascular disease (ASCVD).
• Statins are investigated for ASCVD prevention in PWH, but their effects on inflammatory and cardiovascular proteins are not well understood.
• Understanding these protein changes is crucial for managing cardiovascular risk in PWH.

Purpose of the Study:

• To investigate the effects of pitavastatin on a wide range of plasma proteins in individuals with and without HIV.
• To compare proteomic responses to statin therapy in PWH versus non-HIV participants.
• To identify specific protein alterations related to ASCVD pathways in the context of HIV and statin use.

Main Methods:

• Utilized a discovery proteomic approach (Protein Extension Assay) to analyze over 350 plasma proteins.
• Assessed responses to pitavastatin calcium in 89 PWH (INTREPID trial) and 46 non-HIV participants with metabolic risk factors.
• Excluded individuals with a history of cardiovascular disease from both study groups.

Main Results:

• In PWH, pitavastatin increased PCOLCE and decreased PLA2G7 (a marker of arterial inflammation).
• In non-HIV participants, pitavastatin increased integrin subunit alpha M and defensin alpha-1, and decreased PLA2G7.
• Baseline differences between HIV and non-HIV groups included proteins involved in platelet function, endothelial function, and immune activation.

Conclusions:

• Pitavastatin influences proteins critical for platelet and endothelial function, as well as immune activation.
• The proteomic effects of pitavastatin showed some variations between people with HIV and those without.
• These findings highlight the complex interplay between HIV, statin therapy, and cardiovascular-related protein expression.