Polymorphism in interleukin-7 receptor [alpha] gene is associated with faster CD4+ T-cell recovery after initiation of combination antiretroviral therapy

TY - JOUR

T1 - Polymorphism in interleukin-7 receptor [alpha] gene is associated with faster CD4+ T-cell recovery after initiation of combination antiretroviral therapy

AU - Hartling, Hans Jakob

AU - Thørner, Lise W

AU - Erikstrup, Christian

AU - Harritshøj, Lene H

AU - Kronborg, Gitte

AU - Pedersen, Court

AU - Larsen, Carsten S

AU - Helleberg, Marie

AU - Gerstoft, Jan

AU - Obel, Niels

AU - Ullum, Henrik

AU - Nielsen, Susanne D

PY - 2014/7/31

Y1 - 2014/7/31

N2 - OBJECTIVES: To investigate single-nucleotide polymorphisms (SNPs) in the gene encoding interleukin-7 receptor α (IL7RA) as predictors for CD4⁺ T-cell change after initiation of combination antiretroviral therapy (cART) in HIV-infected whites.DESIGN: SNPs in IL7RA were determined in the Danish HIV Cohort Study.METHODS: CD4⁺ T-cell changes were estimated 6 months, 1, 2, and 5 years after initiation of cART in 1683 HIV-infected virally suppressed individuals. Five SNPs in IL7RA were examined as predictors for CD4⁺ T-cell change in the first (0-6 months after initiation of cART) and second phase (>6 months after initiation of cART) of immune recovery. Univariable and multivariable analyses including age, sex, calendar period, CD4⁺ nadir, and baseline CD4⁺ T-cell count and viral load as covariates were performed.RESULTS: Individuals carrying two T-alleles in rs6897932 had faster CD4⁺ T-cell recovery compared with individuals carrying a C-allele in the first phase of immune recovery [mean CD4⁺ T-cell change, cells/μL (95% confidence interval), in TT: 177 (151-203), CT: 131 (119-143), CC: 141 (132-151), P = 0.018]. No isolated effect of rs6897932 on CD4⁺ T-cell change was found in the second phase of immune recovery; however, the initial difference in CD4⁺ T-cell recovery remained during 5 years. The effect was most pronounced in individuals above 40 years of age.CONCLUSION: T-allele homozygosity in rs6897932 is a predictor for faster CD4⁺ T-cell recovery after initiation of cART in HIV-infected whites, however, only in the first phase of immune recovery.

AB - OBJECTIVES: To investigate single-nucleotide polymorphisms (SNPs) in the gene encoding interleukin-7 receptor α (IL7RA) as predictors for CD4⁺ T-cell change after initiation of combination antiretroviral therapy (cART) in HIV-infected whites.DESIGN: SNPs in IL7RA were determined in the Danish HIV Cohort Study.METHODS: CD4⁺ T-cell changes were estimated 6 months, 1, 2, and 5 years after initiation of cART in 1683 HIV-infected virally suppressed individuals. Five SNPs in IL7RA were examined as predictors for CD4⁺ T-cell change in the first (0-6 months after initiation of cART) and second phase (>6 months after initiation of cART) of immune recovery. Univariable and multivariable analyses including age, sex, calendar period, CD4⁺ nadir, and baseline CD4⁺ T-cell count and viral load as covariates were performed.RESULTS: Individuals carrying two T-alleles in rs6897932 had faster CD4⁺ T-cell recovery compared with individuals carrying a C-allele in the first phase of immune recovery [mean CD4⁺ T-cell change, cells/μL (95% confidence interval), in TT: 177 (151-203), CT: 131 (119-143), CC: 141 (132-151), P = 0.018]. No isolated effect of rs6897932 on CD4⁺ T-cell change was found in the second phase of immune recovery; however, the initial difference in CD4⁺ T-cell recovery remained during 5 years. The effect was most pronounced in individuals above 40 years of age.CONCLUSION: T-allele homozygosity in rs6897932 is a predictor for faster CD4⁺ T-cell recovery after initiation of cART in HIV-infected whites, however, only in the first phase of immune recovery.

U2 - 10.1097/qad.0000000000000354

DO - 10.1097/qad.0000000000000354

M3 - Journal article

C2 - 24911352

SN - 1350-2840

VL - 28

SP - 1739

EP - 1748

JO - AIDS, Supplement

JF - AIDS, Supplement

IS - 12

ER -