Polymorphisms in the CD14 and TLR4 genes independently predict CD4+ T-cell recovery in HIV-infected individuals on antiretroviral therapy

Yong, Y.K. and Shankar, E.M. and Solomon, A. and Spelman, T. and Fairley, C.K. and Elliott, J.H. and Hoy, J. and Cameron, P.U. and Kamarulzaman, A. and Lewin, S.R. (2016) Polymorphisms in the CD14 and TLR4 genes independently predict CD4+ T-cell recovery in HIV-infected individuals on antiretroviral therapy. AIDS, 30 (14). pp. 2159-2168. ISSN 0269-9370, DOI https://doi.org/10.1097/QAD.0000000000001179.

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Official URL: http://dx.doi.org/10.1097/QAD.0000000000001179

Abstract

Background: Chronic HIV infection leads to marked depletion of CD4+ T cells in the gastrointestinal tract and increased microbial translocation measured by an increase in circulating lipopolysaccharide (LPS) levels. Here, we hypothesized that single-nucleotide polymorphisms (SNPs) in genes encoding the Toll-like receptor 4 (TLR4) and CD14, the principal receptors for LPS, were associated with CD4+ T-cell recovery postantiretroviral therapy (ART). Methods: Prospective study of predominantly white HIV-infected participants receiving suppressive ART for at least 12 months. We analysed the CD14 SNPs C-260T and the TLR4 SNPs A+896G, C+1196T. We also determined the levels of LPS and soluble CD14 in plasma samples collected pre-ART and post-ART initiation. CD4+ T-cell recovery was assessed by linear mixed models. Results: Following ART, individuals with a TT genotype compared with a CT or CC genotype for CD14 C-260T SNP showed higher levels of soluble CD14 (P = 0.008 and 0.003, respectively). The CC genotype for the CD14 C-260T SNP, compared with CT or TT, and the TLR4 SNP (AC/GT), compared with the homozygous genotype (AA/CC), were both independently associated with enhanced long-term CD4+ T-cell recovery (>3 months; P < 0.001). Conclusion: Polymorphisms in CD14 and TLR4 are independently associated with long-term CD4+ T-cell recovery in HIV-infected individuals post-ART.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: C-260T CD14 single-nucleotide polymorphism; CD4+ cell count recovery; HIV; Lipopolysaccharide; Microbial translocation; Soluble CD14
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 30 May 2018 04:47
Last Modified: 30 May 2018 04:47
URI: http://eprints.um.edu.my/id/eprint/18760

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