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接受抗逆转录病毒治疗的艾滋病毒合并丙型肝炎病毒感染患者中丙型肝炎病毒的演变

Evolution of hepatitis C virus in HIV coinfected patients under antiretroviral therapy.

作者信息

Sede Mariano, Parra Micaela, Manrique Julieta M, Laufer Natalia, Jones Leandro R, Quarleri Jorge

机构信息

Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina; Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155-Piso 11, C1121ABG Buenos Aires, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1083ACA Buenos Aires, Argentina; Laboratorio de Virología y Genética Molecular, Facultad de Ciencias Naturales sede Trelew, Universidad Nacional de la Patagonia San Juan Bosco, 9 de Julio y Belgrano S/N, 9100 Trelew, Chubut, Argentina.

出版信息

Infect Genet Evol. 2016 Sep;43:186-96. doi: 10.1016/j.meegid.2016.05.032. Epub 2016 May 24.

Abstract

Five patients (P) were followed-up for an average of 7.73years after highly active antiretroviral therapy (HAART) initiation. Patients' immune and virological status were determined by periodical CD4+T-cell counts and HIV and HCV viral load. HCV populations were studied using longitudinal high throughput sequence data obtained in parallel by virological and immunological parameters. Two patients (P7, P28) with sub-optimal responses to HAART presented HCV viral loads significantly higher than those recorded for two patients (P1, P18) that achieved good responses to HAART. Interestingly, HCV populations from P7 and P28 displayed a stable phylogenetic structure, whereas HCV populations from P1 and P18showeda significant increase in their phylogenetic structure, followed by a decrease after achieving acceptable CD4+T-cell counts (>500 cell/μl). The fifth patient (P25) presented high HCV viral loads, preserved CD4+T-cell counts from baseline and all along the follow-up, and displayed a constant viral phylogenetic structure. These results strongly suggest that HAART-induced immune recovery induces a decrease in HCV viral load and an increase in the HCV population phylogenetic structure likely reflecting the virus diversification in response to the afresh immune response. The relatively low HCV viral load observed in the HAART responder patients suggests that once HCV is adapted it reaches a maximum number of haplotypes higher than that achieved during the initial stages of the immune response as inferred from the two recovering patients. Future studies using larger number of patients are needed to corroborate these hypotheses.

摘要

5名患者(P)在开始高效抗逆转录病毒治疗(HAART)后平均随访了7.73年。通过定期检测CD4+T细胞计数以及HIV和HCV病毒载量来确定患者的免疫和病毒学状态。利用通过病毒学和免疫学参数并行获得的纵向高通量序列数据研究HCV群体。两名对HAART反应欠佳的患者(P7、P28)的HCV病毒载量显著高于两名对HAART反应良好的患者(P1、P18)的记录值。有趣的是,P7和P28的HCV群体呈现出稳定的系统发育结构,而P1和P18的HCV群体在系统发育结构上显著增加,在CD4+T细胞计数达到可接受水平(>500个细胞/μl)后下降。第五名患者(P25)的HCV病毒载量较高,从基线到整个随访期间CD4+T细胞计数保持不变,并且呈现出恒定的病毒系统发育结构。这些结果强烈表明,HAART诱导的免疫恢复导致HCV病毒载量下降以及HCV群体系统发育结构增加,这可能反映了病毒为应对新的免疫反应而发生的多样化。在HAART反应良好的患者中观察到的相对较低的HCV病毒载量表明,一旦HCV适应,其单倍型数量达到最大值,高于从两名恢复患者推断出的免疫反应初始阶段所达到的数量。需要使用更多患者进行未来研究以证实这些假设。

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