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

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 JH, Hoy J, Cameron PU, Kamarulzaman A, Lewin SR,


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

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

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AIDS (London, England) 30(14) 2159-68 doi 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.

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