Assessing statin effects on cardiovascular pathways in HIV using a novel proteomics approach: Analysis of data from INTREPID, a randomized controlled trial

EBioMedicine
Mabel ToribioSteven K Grinspoon

Abstract

People with HIV (PWH) demonstrate increased cardiovascular disease (CVD), due in part to increased immune activation, inflammation, and endothelial dysfunction. In a randomized trial (INTREPID), 252 HIV-infected participants with dyslipidemia and no history of coronary artery disease were randomized (1:1) to pitavastatin 4 mg vs. pravastatin 40 mg for 52 weeks. Using a proteomic discovery approach, 92 proteins biomarkers were assessed using Proximity Extension Assay technology to determine the effects of statins on key atherosclerosis and CVD pathways among PWH. 225 participants had specimens available for biomarker analysis pre- and post-baseline. The mean age was 49.5 ± 8.0 (mean ± SD), LDL-C 155 ± 25 mg/dl and CD4 count 620 ± 243 cell/mm3. Among all participants, three proteins significantly decreased: tissue factor pathway inhibitor [TFPI; t-statistic = -6.38, FDR p-value<0.0001], paraoxonase 3 [PON3; t-statistic = -4.64, FDR p-value = 0.0003], and LDL-receptor [LDLR; t-statistic = -4.45, FDR p-value = 0.0004]; and two proteins significantly increased galectin-4 [Gal-4; t-statistic = 3.50, FDR p-value = 0.01] and insulin-like growth factor binding protein 2 [IGFBP-2; t-statistic = 3.21, FDR p-value = 0.03]. The change in TF...Continue Reading

Citations

Jul 19, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Alison C KearnsXuebin Qin 秦学斌
Jul 25, 2019·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Roger J BedimoUNKNOWN A5321 Study Team
Oct 31, 2020·The Journal of Clinical Endocrinology and Metabolism·Takara L StanleySteven K Grinspoon

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Methods Mentioned

BETA
Assay

Clinical Trials Mentioned

NCT01301066
NCT02344290

Software Mentioned

SAS JMP
INTREPID
SAS

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