LIR, NIAID, NIH, DHHS, Bethesda, Maryland, USA.
AIDS. 2011 Jun 1;25(9):1179-87. doi: 10.1097/QAD.0b013e3283471d53.
Hepatitis C virus (HCV)/HIV co-infected patients have more rapid progression of liver fibrosis and only modest cure rates (sustained virologic responses, SVRs) when compared to HCV monoinfected patients.
We compared the virologic responses of either twice-weekly peginterferon-α-2a 180 μg/week (for 4 weeks, followed by weekly dosing) or weekly peginterferon-α-2a 180 μg/week, and weight-based ribavirin (1-1.2 g/day), among HIV/HCV co-infected genotype-1 individuals.
Patients receiving the investigational dosing had lower levels of HCV RNA at all time points after initiation of therapy. More patients on this arm achieved clinically relevant early virological responses at weeks 1, 2, 4, 12, and 24. The enhanced early virologic response observed with the investigational arm was associated with a higher induction of interferon-stimulated genes. This early double dose regimen also resulted in a rapid normalization of liver enzymes. Twice-weekly peginterferon-α-2a was associated with more frequent early virological responses with similar safety profiles when compared with standard therapy.
Our results, when confirmed in larger randomized clinical trials, may provide a novel therapeutic approach to improve SVR among HIV/HCV co-infected patients, especially African-American patients.
与 HCV 单感染患者相比,HCV/HIV 合并感染患者的肝纤维化进展更快,且仅有适度的治愈率(持续病毒学应答,SVR)。
我们比较了每周一次的聚乙二醇干扰素-α-2a 180μg/周(4 周后每周一次)或每周一次的聚乙二醇干扰素-α-2a 180μg/周,以及基于体重的利巴韦林(1-1.2g/天)在 HIV/HCV 合并感染基因型 1 个体中的病毒学反应。
接受研究性剂量的患者在治疗开始后的所有时间点的 HCV RNA 水平均较低。更多接受该治疗组的患者在第 1、2、4、12 和 24 周时达到了有临床意义的早期病毒学应答。研究组观察到的增强的早期病毒学应答与干扰素刺激基因的更高诱导相关。这种早期双倍剂量方案还导致肝酶迅速正常化。与标准治疗相比,每周两次的聚乙二醇干扰素-α-2a 与更频繁的早期病毒学应答相关,且安全性相似。
我们的研究结果,如果在更大规模的随机临床试验中得到证实,可能为改善 HIV/HCV 合并感染患者,特别是非裔美国患者的 SVR 提供一种新的治疗方法。