Affiliations 

  • 1 aCentre of Excellence for Research in AIDS (CERiA) bTropical Infectious Diseases Research and Education Centre (TIDREC), Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia cCentre for Biomedical Research dCentre for Population Health, Burnet Institute eDepartment of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia fInfectious Disease Unit, University Malaya Medical Centre, Kuala Lumpur, Malaysia gPeter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia hDivision of Infection Biology and Microbiology, Department of Life Sciences, School of Basic and Applied Sciences, Central University of Tamil Nadu (CUTN), Neelakudi Campus, Tiruvarur, India
Medicine (Baltimore), 2016 Aug;95(31):e4477.
PMID: 27495090 DOI: 10.1097/MD.0000000000004477

Abstract

HIV-infected individuals on antiretroviral therapy (ART) are at increased risk of cardiovascular disease (CVD). Given the relationship between innate immune activation and CVD, we investigated the association of single-nucleotide polymorphisms (SNPs) in TLR4 and CD14 and carotid intima-media thickness (cIMT), a surrogate measurement for CVD, in HIV-infected individuals on ART and HIV-uninfected controls as a cross-sectional, case-control study. We quantified the frequency of monocyte subsets (CD14, CD16), markers of monocyte activation (CD38, HLA-DR), and endothelial adhesion (CCR2, CX3CR1, CD11b) by flow cytometry. Plasma levels of lipopolysaccharide, sCD163, sCD14, sCX3CL1, and sCCL2, were measured by ELISA. Genotyping of TLR4 and CD14 SNPs was also performed. The TT genotype for CD14/-260SNP but not the CC/CT genotype was associated with elevated plasma sCD14, and increased frequency of CD11b+CD14+ monocytes in HIV-infected individuals. The TT genotype was associated with lower cIMT in HIV-infected patients (n = 47) but not in HIV-uninfected controls (n = 37). The AG genotype for TLR4/+896 was associated with increased CX3CR1 expression on total monocytes among HIV-infected individuals and increased sCCL2 and fibrinogen levels in HIV-uninfected controls. SNPs in CD14/-260 and TLR4/+896 were significantly associated with different markers of systemic and monocyte activation and cIMT that differed between HIV-infected participants on ART and HIV-uninfected controls. Further investigation on the relationship of these SNPs with a clinical endpoint of CVD is warranted in HIV-infected patients on ART.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.