DBP rs7041 and DHCR7 rs3829251 are linked to CD4+ recovery in HIV patients on antiretroviral therapy

Background: The lack of the recovery of CD4+ T-cells (CD4+ recovery) among immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is not well known. We aimed to analyze the association between single nucleotide polymorphisms (SNPs) underlying vitamin D metabolism and the CD4+ recovery in naïve HIV-infected patients who started ART with low baseline CD4+. Methods: We conducted a retrospective study in 411 naïve individuals with plasma HIV load >200 copies/mL and CD4+ <200 cells/mm3. During 24 months of follow-up, all patients had plasma HIV load <50 copies/mL. DNA genotyping was performed using the Sequenom MassARRAY platform. The outcome variable was the change in CD4+ during the study. Results: CD4+ recovery was higher in patients carrying DBP rs7041 AA genotype (AA versus CC/AC) and DHCR7 rs3829251 AA genotype (AA versus GG/AG) (p-value <0.05). DBP rs7041 AA genotype was linked to increase in CD4+ (adjusted arithmetic mean ratio (aAMR)=1.22; q-value=0.011), increase in CD4+ ≥P75th (adjusted odds ratio (aOR)=2.31; q-value=0.005), slope of CD4+ recovery (aAMR=1.25; q-value=0.008), slope of CD4+ recovery ≥P75th (aOR=2.55; q-value=0.005) and achievement of CD4+ ≥500 cells/mm3 (aOR=1.89; q-value=0.023). Besides, DHCR7 rs3829251 AA genotype was related to increase in CD4+ (aAMR=1.43; q-value=0.031), increase in CD4+ ≥P75th (aOR=3.92; q-value=0.030), slope of CD4+ recovery (aAMR=1.40; q-value=0.036), slope of CD4+ recovery ≥P75th (aOR=3.42; q-value=0.031) and achievement of CD4+ ≥500 cells/mm3 (aOR=5.68; q-value=0.015). Conclusion: DHCR7 rs3829251 and DBP rs7041 polymorphisms were associated with the CD4+ recovery. More studies are needed to understand the impact of these SNPs on CD4+ recovery in HIV-infected late presenter patients.背景：接受抗逆转录病毒治疗（antiretroviral therapy, ART）的人类免疫缺陷病毒（immunodeficiency virus, HIV）感染者中，CD4+T淋巴细胞（CD4+ T-cells）恢复不足的现象尚未得到充分阐释。本研究旨在探讨参与维生素D代谢（vitamin D metabolism）的单核苷酸多态性（single nucleotide polymorphisms, SNPs）与基线CD4+细胞计数较低的初治HIV感染者接受ART后CD4+恢复情况的关联。 方法：本研究为回顾性研究，纳入411例初治HIV感染者，其基线血浆HIV病毒载量>200拷贝/mL且CD4+细胞计数<200个/mm³。在24个月的随访周期内，所有患者的血浆HIV病毒载量均降至<50拷贝/mL。采用Sequenom MassARRAY平台完成DNA基因分型检测。本研究的结局变量为研究期间CD4+细胞计数的变化情况。 结果：携带DBP rs7041 AA基因型（AA vs CC/AC）与DHCR7 rs3829251 AA基因型（AA vs GG/AG）的患者，其CD4+恢复水平显著更高（P值<0.05）。其中，DBP rs7041 AA基因型与以下指标相关：CD4+细胞计数升高（校正算术均数比（adjusted arithmetic mean ratio, aAMR）=1.22；q值=0.011）、CD4+细胞计数升高幅度达第75百分位数以上（校正比值比（adjusted odds ratio, aOR）=2.31；q值=0.005）、CD4+恢复斜率升高（aAMR=1.25；q值=0.008）、CD4+恢复斜率达第75百分位数以上（aOR=2.55；q值=0.005）以及CD4+细胞计数达到≥500个/mm³（aOR=1.89；q值=0.023）。此外，DHCR7 rs3829251 AA基因型与CD4+细胞计数升高（aAMR=1.43；q值=0.031）、CD4+细胞计数升高幅度达第75百分位数以上（aOR=3.92；q值=0.030）、CD4+恢复斜率升高（aAMR=1.40；q值=0.036）、CD4+恢复斜率达第75百分位数以上（aOR=3.42；q值=0.031）以及CD4+细胞计数达到≥500个/mm³（aOR=5.68；q值=0.015）显著相关。 结论：DHCR7 rs3829251与DBP rs7041基因多态性与HIV感染者的CD4+恢复情况存在关联。未来仍需开展更多研究，以明确上述单核苷酸多态性对HIV感染晚就诊患者CD4+恢复的影响。