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

Hartling, Hans J.a,b,c; Thørner, Lise W.c; Erikstrup, Christiand; Harritshøj, Lene H.c; Kronborg, Gittee; Pedersen, Courtf; Larsen, Carsten S.g; Helleberg, Mariea; Gerstoft, Jana; Obel, Nielsa; Ullum, Henrikc; Nielsen, Susanne D.a,b

doi: 10.1097/QAD.0000000000000354
Basic Science

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.

aDepartment of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

bViro-Immunology Research Unit

cDepartment of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen

dDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus

eDepartment of Infectious Diseases, Hvidovre, Copenhagen University Hospital, Copenhagen

fDepartment of Infectious Diseases, Odense University Hospital, Odense

gDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Correspondence to Susanne D. Nielsen, Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark. Tel: +45 35 45 08 59; e-mail: sdn@dadlnet.dk

Received 3 December, 2013

Revised 17 May, 2014

Accepted 19 May, 2014

© 2014 Lippincott Williams & Wilkins, Inc.