Hartling Hans J, Thørner Lise W, Erikstrup Christian, Harritshøj Lene H, Kronborg Gitte, Pedersen Court, Larsen Carsten S, Helleberg Marie, Gerstoft Jan, Obel Niels, Ullum Henrik, Nielsen Susanne D
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.
AIDS. 2014 Jul 31;28(12):1739-48. doi: 10.1097/QAD.0000000000000354.
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.
SNPs in IL7RA were determined in the Danish HIV Cohort Study.
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.
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.
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.
研究白细胞介素-7受体α（IL7RA）编码基因中的单核苷酸多态性（SNP），作为预测HIV感染的白人开始联合抗逆转录病毒治疗（cART）后CD4⁺ T细胞变化的指标。
在丹麦HIV队列研究中确定IL7RA中的SNP。
在1683例HIV感染且病毒得到抑制的个体中，估计开始cART后6个月、1年、2年和5年时的CD4⁺ T细胞变化。检测IL7RA中的5个SNP，作为免疫恢复第一阶段（开始cART后0 - 6个月）和第二阶段（开始cART后>6个月）CD4⁺ T细胞变化的预测指标。进行单变量和多变量分析，将年龄、性别、日历时间、CD4⁺最低点、基线CD4⁺ T细胞计数和病毒载量作为协变量。
在免疫恢复的第一阶段，与携带C等位基因的个体相比，rs6897932中携带两个T等位基因的个体CD4⁺ T细胞恢复更快[TT基因型的平均CD4⁺ T细胞变化，细胞/μL（95%置信区间）：177（151 - 203），CT基因型：131（119 - 143），CC基因型：141（132 - 151），P = 0.018]。在免疫恢复的第二阶段未发现rs6897932对CD4⁺ T细胞变化有单独影响；然而，CD4⁺ T细胞恢复的初始差异在5年期间持续存在。这种影响在40岁以上的个体中最为明显。
rs6897932中的T等位基因纯合性是HIV感染的白人开始cART后CD4⁺ T细胞更快恢复的预测指标，然而，仅在免疫恢复的第一阶段如此。
