School of Medicine, Nankai University, Tianjin, China.
State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Clin Infect Dis. 2021 May 18;72(10):1799-1809. doi: 10.1093/cid/ciaa380.
Human immunodeficiency virus type 1 (HIV-1) clades and clusters have different epidemic patterns and phenotypic profiles. It is unclear if they also affect patients' immune recovery (IR) in combination antiretroviral therapy (cART).
We conducted a cohort study on 853 patients under cART for evaluating the impacts of viral factor on host IR. We used generalized estimating equations for factors affecting CD4 recovery, Kaplan-Meier curves for probability of achieving IR, and Cox hazards model for factors influencing IR capability.
Besides low baseline CD4 and old age, CRF01_AE and its cluster 4 were independently associated with lower CD4 cell level (P ≤ .003), slower IR (P ≤ .022), fewer patients (P < .001), and longer time achieving IR (P < .001), compared with CRF07_BC and CRF01_AE cluster 5. Higher percentage of CXCR4 (X4) viruses in the CRF01_AE and cluster 4-infected patients, compared with their respective counterparts (P < .001), accounted for the poor IR in infected patients (P < .001). Finally, we revealed that greater X4 receptor binding propensity of amino acids was exhibited in CRF01_AE clade (P < .001) and its cluster 4 (P ≤ .004).
Our study demonstrates that the CRF01_AE clade and cluster are associated with poor IR in patients under cART, which is ascribed to a high proportion of viruses with X4 tropism. HIV-1 genotyping and phenotyping should be used as a surveillance tool for patients initiating cART. CCR5 inhibitors should be used with caution in regions with high prevalence of X4 viruses.
人类免疫缺陷病毒 1 型（HIV-1）的亚型和簇具有不同的流行模式和表型特征。目前尚不清楚它们是否也会影响接受联合抗逆转录病毒治疗（cART）的患者的免疫恢复（IR）。
我们对 853 名接受 cART 的患者进行了一项队列研究，以评估病毒因素对宿主 IR 的影响。我们使用广义估计方程评估影响 CD4 恢复的因素，Kaplan-Meier 曲线评估实现 IR 的概率，Cox 风险模型评估影响 IR 能力的因素。
除了基线 CD4 较低和年龄较大外，CRF01_AE 及其簇 4 与较低的 CD4 细胞水平（P ≤.003）、较慢的 IR（P ≤.022）、较少的患者（P <.001）和更长的时间达到 IR（P <.001）独立相关，与 CRF07_BC 和 CRF01_AE 簇 5 相比。CRF01_AE 和簇 4 感染患者中 CXCR4（X4）病毒的百分比较高（P <.001），与各自的病毒相比，这导致了感染患者的 IR 不良（P <.001）。最后，我们发现 CRF01_AE 分支（P <.001）及其簇 4（P ≤.004）中 X4 受体结合倾向的氨基酸更大。
我们的研究表明，在接受 cART 的患者中，CRF01_AE 亚群和簇与 IR 不良相关，这归因于高比例具有 X4 嗜性的病毒。HIV-1 基因分型和表型分析应作为启动 cART 的患者的监测工具。在 X4 病毒流行率较高的地区，应谨慎使用 CCR5 抑制剂。
