Klinik und Poliklinik für Infektiologie, University Hospital Berne and University of Berne, Inselspital PKT2B, 3010 Bern, Switzerland.
Gut. 2010 Sep;59(9):1252-8. doi: 10.1136/gut.2009.205971. Epub 2010 Jul 26.
Hepatitis C virus (HCV) infection is a major cause of morbidity in HIV infected individuals. Coinfection with HIV is associated with diminished HCV-specific immune responses and higher HCV RNA levels.
To investigate whether long-term combination antiretroviral therapy (cART) restores HCV-specific T cell responses and improves the control of HCV replication.
T cell responses were evaluated longitudinally in 80 HIV/HCV coinfected individuals by ex vivo interferon-gamma-ELISpot responses to HCV core peptides, that predominantly stimulate CD4(+) T cells. HCV RNA levels were assessed by real-time PCR in 114 individuals.
The proportion of individuals with detectable T cell responses to HCV core peptides was 19% before starting cART, 24% in the first year on cART and increased significantly to 45% and 49% after 33 and 70 months on cART (p=0.001). HCV-specific immune responses increased in individuals with chronic (+31%) and spontaneously cleared HCV infection (+30%). Median HCV RNA levels before starting cART were 6.5 log(10) IU/ml. During long-term cART, median HCV-RNA levels slightly decreased compared to pre-cART levels (-0.3 log10 IU/ml, p=0.02).
Successful cART is associated with increasing cellular immune responses to HCV core peptides and with a slight long-term decrease in HCV RNA levels. These findings are in line with the favourable clinical effects of cART on the natural history of hepatitis C and with the current recommendation to start cART earlier in HCV/HIV coinfected individuals.
丙型肝炎病毒(HCV)感染是 HIV 感染者发病的主要原因。HIV 合并感染与 HCV 特异性免疫应答减弱和 HCV RNA 水平升高有关。
研究长期联合抗逆转录病毒治疗(cART)是否恢复 HCV 特异性 T 细胞应答并改善 HCV 复制的控制。
通过 HCV 核心肽的体外干扰素-γ-ELISpot 反应,对 80 例 HIV/HCV 合并感染患者进行了纵向 T 细胞应答评估,这些肽主要刺激 CD4+T 细胞。通过实时 PCR 评估了 114 例患者的 HCV RNA 水平。
在开始 cART 之前,有检测到 HCV 核心肽 T 细胞应答的个体比例为 19%,在开始 cART 的第一年增加到 24%,在开始 cART 33 个月和 70 个月后分别显著增加到 45%和 49%(p=0.001)。慢性(+31%)和自发性清除 HCV 感染(+30%)患者的 HCV 特异性免疫应答增加。开始 cART 前的 HCV RNA 水平中位数为 6.5 log10 IU/ml。在长期 cART 期间,与 cART 前水平相比,HCV-RNA 水平中位数略有下降(-0.3 log10 IU/ml,p=0.02)。
成功的 cART 与 HCV 核心肽的细胞免疫应答增加以及 HCV RNA 水平的长期轻度下降相关。这些发现与 cART 对丙型肝炎自然史的有利临床影响以及目前建议在 HCV/HIV 合并感染患者中更早开始 cART 一致。