Unit of HIV/Hepatitis Coinfection, National Centre of Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
J Antimicrob Chemother. 2013 Oct;68(10):2349-57. doi: 10.1093/jac/dkt206. Epub 2013 Jun 7.
There is substantial interindividual variability in the rate and extent of CD4+ T cell recovery after starting combination antiretroviral therapy (cART). The aim of our study was to determine whether mitochondrial DNA (mtDNA) haplogroups are associated with recovery of CD4+ in HIV-infected patients on cART.
We carried out a retrospective study on 275 cART-naive patients with CD4+ counts <350 cells/mm(3), who were followed-up during at least 24 months after initiating cART. mtDNA genotyping was performed by Sequenom's MassARRAY platform.
Patients within cluster JT and haplogroup J had a lower chance of achieving a CD4+ count ≥500 cells/mm(3) than patients within cluster HV and haplogroup H [hazard ratio (HR) = 0.68 (P = 0.058) and HR = 0.48 (P = 0.010), respectively]. The time of follow-up during which the CD4+ count was ≥500 cells/mm(3) was longer in haplogroups HV and H than in haplogroups JT and J [20 months versus 6.2 months (P = 0.029) and 20 months versus 0 months (P = 0.024), respectively]. Additionally, haplogroups HV and H had greater chances of achieving a CD4+ count ≥500 cells/mm(3) during at least 12, 36, 48 and 60 months post-cART initiation compared with patients within haplogroups JT and J. Patients within haplogroup T only had a lesser chance of achieving a CD4+ count ≥500 cells/mm(3) during at least 48 months and 60 months post-cART initiation.
European mitochondrial haplogroups might influence CD4+ recovery in HIV-infected patients following initiation with cART. Haplogroups J and T appear to be associated with a worse profile of CD4+ recovery, whereas haplogroup H was associated with a better CD4+ reconstitution.
在开始联合抗逆转录病毒治疗(cART)后,CD4+T 细胞恢复的速度和程度存在很大的个体间差异。我们的研究目的是确定线粒体 DNA(mtDNA)单倍群是否与接受 cART 的 HIV 感染患者的 CD4+恢复有关。
我们对 275 名 CD4+计数<350 个细胞/mm3 的 cART 初治患者进行了回顾性研究,这些患者在开始 cART 后至少随访 24 个月。mtDNA 基因分型采用 Sequenom 的 MassARRAY 平台进行。
与 HV 集群和 H 单倍群患者相比,JT 集群和 J 单倍群患者达到 CD4+计数≥500 个细胞/mm3 的机会较低[风险比(HR)=0.68(P=0.058)和 HR=0.48(P=0.010)]。HV 和 H 单倍群患者的 CD4+计数≥500 个细胞/mm3 的随访时间长于 JT 和 J 单倍群患者[20 个月比 6.2 个月(P=0.029)和 20 个月比 0 个月(P=0.024)]。此外,与 JT 和 J 单倍群患者相比,HV 和 H 单倍群患者在 cART 开始后至少 12、36、48 和 60 个月时达到 CD4+计数≥500 个细胞/mm3 的机会更大。与其他单倍群患者相比,仅 T 单倍群患者在 cART 开始后至少 48 个月和 60 个月时达到 CD4+计数≥500 个细胞/mm3 的机会较低。
欧洲线粒体单倍群可能影响接受 cART 治疗的 HIV 感染患者的 CD4+恢复。J 和 T 单倍群似乎与 CD4+恢复的不良预后相关,而 H 单倍群与更好的 CD4+重建相关。