Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Spain.
HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain.
Biomolecules. 2019 Jun 16;9(6):233. doi: 10.3390/biom9060233.
Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 polymorphism is related to CD4 recovery after combination antiretroviral therapy (cART), but no studies so far have analyzed its potential impact in patients with very low CD4 T-cells count. We aimed to analyze the association between rs6897932 polymorphism and CD4 T-cells count restoration in HIV-infected patients starting combination antiretroviral therapy (cART) with CD4 T-cells count <200 cells/mm. We performed a retrospective study in 411 patients followed for 24 months with a DNA sample available for genotyping. The change in CD4 T-cells count during the follow-up was considered as the primary outcome. The rs6897932 polymorphism had a minimum allele frequency (MAF) >20% and was in Hardy-Weinberg equilibrium ( = 0.550). Of 411 patients, 256 carried the CC genotype, while 155 had the CT/TT genotype. The CT/TT genotype was associated with a higher slope of CD4 T-cells recovery (arithmetic mean ratio; AMR = 1.16; = 0.016), higher CD4 T-cells increase (AMR = 1.19; = 0.004), and higher CD4 T-cells count at the end of follow-up (AMR = 1.13; = 0.006). Besides, rs6897932 CT/TT was related to a higher odds of having a value of CD4 T-cells at the end of follow-up ≥500 CD4 cells/mm (OR = 2.44; = 0.006). After multiple testing correction (Benjamini-Hochberg), only the increase of ≥ 400 CD4 cells/mm lost statistical significance ( = 0.052). rs6897932 CT/TT genotype was related to a better CD4 T-cells recovery and it could be used to improve the management of HIV-infected patients starting cART with CD4 T-cells count <200 cells/mm.
白细胞介素 7 受体亚单位 α(IL7RA)rs6897932 多态性与联合抗逆转录病毒治疗(cART)后 CD4 恢复有关,但迄今为止尚无研究分析其在 CD4 T 细胞计数极低的患者中的潜在影响。我们旨在分析 rs6897932 多态性与开始 cART 时 CD4 T 细胞计数<200 个/毫米的 HIV 感染患者的 CD4 T 细胞计数恢复之间的关联。我们对 411 名接受 24 个月随访并可进行基因分型的患者进行了回顾性研究。将随访期间 CD4 T 细胞计数的变化作为主要结局。rs6897932 多态性的最小等位基因频率(MAF)>20%,处于 Hardy-Weinberg 平衡(=0.550)。在 411 名患者中,256 名患者携带 CC 基因型,而 155 名患者携带 CT/TT 基因型。CT/TT 基因型与 CD4 T 细胞恢复的斜率更高相关(算术平均值比;AMR=1.16;=0.016),CD4 T 细胞增加更多(AMR=1.19;=0.004),随访结束时 CD4 T 细胞计数更高(AMR=1.13;=0.006)。此外,rs6897932 CT/TT 与随访结束时 CD4 T 细胞计数≥500 个/毫米的可能性更高相关(比值比;OR=2.44;=0.006)。经过多重测试校正(Benjamini-Hochberg),只有增加≥400 个/毫米的 CD4 细胞失去统计学意义(=0.052)。rs6897932 CT/TT 基因型与 CD4 T 细胞恢复更好相关,可用于改善开始 cART 时 CD4 T 细胞计数<200 个/毫米的 HIV 感染患者的管理。