ICMR-National AIDS Research Institute, 73-G block, M.I.D.C, Bhosari, Pune, India.
ICMR-National AIDS Research Institute, 73-G block, M.I.D.C, Bhosari, Pune, India.
Microb Pathog. 2020 Jun;143:104117. doi: 10.1016/j.micpath.2020.104117. Epub 2020 Mar 3.
Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40). They were assessed for HIV drug resistance by sequencing, plasma cytokines by luminex assay, T cell activation status by flow cytometry and total IgE levels by ELISA. VNR and failure patients had significantly lower median baseline CD4 counts than the responders. VNRs had significantly higher CD4 counts but lower viral load than treatment failures at one year of ART. VNRs had the highest eosinophil counts and the highest IL-5 levels among all the groups. IL-5 levels in them correlated with their viral load values. Frequency of Treg cells was also highest among the VNR group participants. More than 60% of the viremic patients irrespective of their groups harboured multiple HIV drug resistance mutations and mutation pattern did not differ between the groups. Low baseline CD4 counts and presence of multiple drug resistance mutations in the viremic groups highlighted the importance of early ART initiation and viral load monitoring irrespective of presence of immunologic failure. High IL-5 levels in VNR group indicated a need for investigating causal relationship between IL-5 and viral replication to devise therapeutic strategies to control viremia.
在低收入国家,接受抗逆转录病毒治疗的 HIV 感染患者中缺乏病毒监测,可能会漏掉尽管病毒复制未被抑制但免疫却得到恢复的病毒学无应答者(VNR)。需要研究这些不相符的患者与相符的治疗失败组之间的生物标志物和耐药模式,以了解与这种情况相关的可能危险因素。将接受抗逆转录病毒治疗一年的 HIV 感染患者分为三组,即 VNR(n=25)、治疗失败(n=18)和治疗应答者(n=40)。通过测序评估 HIV 耐药性,通过 Luminex 检测评估血浆细胞因子,通过流式细胞术评估 T 细胞激活状态,通过 ELISA 评估总 IgE 水平。VNR 和失败患者的基线 CD4 计数中位数明显低于应答者。在接受 ART 治疗一年时,VNR 患者的 CD4 计数明显较高,但病毒载量低于治疗失败患者。VNR 患者的嗜酸性粒细胞计数和 IL-5 水平最高,且在所有组中均高于治疗失败患者。IL-5 水平与他们的病毒载量值相关。Treg 细胞的频率在 VNR 组参与者中也是最高的。超过 60%的病毒血症患者,无论其组如何,均携带多种 HIV 耐药突变,且各组之间的突变模式没有差异。病毒血症组中低基线 CD4 计数和存在多种耐药突变突出强调了早期开始 ART 和病毒载量监测的重要性,而与免疫失败的存在无关。VNR 组中高 IL-5 水平表明需要调查 IL-5 与病毒复制之间的因果关系,以制定控制病毒血症的治疗策略。