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

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Yong YK, Shankar EM, Solomon A, Spelman T, Fairley CK, Elliott J, Hoy J, Cameron P, Kamarulzaman A, Lewin SR,


Yong YK, Shankar EM, Solomon A, Spelman T, Fairley CK, Elliott J, Hoy J, Cameron P, Kamarulzaman A, Lewin SR, (click to view)

Yong YK, Shankar EM, Solomon A, Spelman T, Fairley CK, Elliott J, Hoy J, Cameron P, Kamarulzaman A, Lewin SR,

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AIDS (London, England) 2016 6 8()

Abstract
BACKGROUND
Chronic HIV infection leads to marked depletion of CD4+ T cells in the gastrointestinal (GI) tract and increased microbial translocation measured by an increase in circulating lipopolysaccharide (LPS) levels. Here, we hypothesised 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 post-antiretroviral therapy (ART).

METHODS
Prospective study of predominantly Caucasian HIV-infected subjects 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 (sCD14) in plasma samples collected pre- and post-ART initiation. CD4+ T-cell recovery was assessed by linear mixed models.

RESULTS
Following ART, individuals with a TT genotype compared to a CT or CC genotype for CD14 C-260T SNP showed higher levels of sCD14 (p=0.008 and 0.003 respectively). The CC genotype for the CD14 C-260T SNP, compared to CT or TT and the TLR4 SNP (AC/GT) compared to the homozygous genotype (AA/CC) were both independently associated with enhanced long-term CD4+ T-cell recovery (>3 months; p<0.001). CONCLUSIONS
Polymorphisms in CD14 and TLR4 are independently associated with long-term CD4+ T-cell recovery in HIV-infected individuals post-ART.

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