Resistance-associated mutations to HCV protease inhibitors naturally pre-existed in HIV/HCV coinfected, treatment-naïve patients

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• 作者：Ying Cao^a ; Yi Bao^a ; ^b ; Wei Xia^c ; Hao Wu^c ; Feili Wei^c ; Yu Zhang^a ; Renwen Zhang^a ; Xiaoyuan Xu^a ; ^{xiaoyuanxu6@163.com" class="auth_mail" title="E-mail the corresponding author}
• 刊名：Clinics and Research in Hepatology and Gastroenterology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：40
• 期：5
• 页码：597-604
• 全文大小：656 K

文摘

Presently, it has been approved to treat hepatitis C virus (HCV) infection with protease inhibitors (PIs). In the present study, we aimed to illustrate the natural prevalence of HCV NS3/4A PI resistance mutations in HIV/HCV coinfected, treatment-naïve patients.

Methods

Population sequence analysis of the NS3/4A protease was conducted in 96 HIV/HCV coinfected, treatment-naïve patients.

Results

Complete HCV NS3/4A sequence information was obtained from 70 (72.92%) samples, including 68 patients (97.14%) with genotype 1b and 2 patients (2.86%) with genotype 2a. A total of 21 patients (30.88%) of the 68 patients with HCV genotype 1b showed amino acid substitutions associated with HCV PI resistance. Mutation F43S was observed in 1.47% of patients with genotype 1b. The mutations of T54S, Q80K/R, R155K, A156G and D168A/E/G were found in 4.41%, 1.47%/1.47%, 2.94%, 23.53% and 1.47%/1.47%/1.47% of patients with genotype 1b, respectively. In addition, 4.41% of patients with genotype 1b showed double mutations in the NS3 region. The multiple mutations of Q80R + R155K + D168G and Q80K + R155K + A156G + D168A were detected in 1.47% and 1.47% of patients with HCV genotype 1b, respectively.

Conclusions

The most predominant HCV genotype was 1b in patients with HIV/HCV coinfection. Naturally occurring mutations resistant to HCV PIs (simeprevir, vaniprevir, boceprevir, telaprevir, asunaprevir and paritaprevir) pre-existed in patients with HIV/HCV genotype 1b coinfection. The effects of baseline PI resistance on treatment outcome should be further analyzed.