标题：Low frequency of drug-resistant virus did not affect the therapeutic efficacy in daclatasvir plus asunaprevir therapy in patients with chronic HCV genotype 1 infection

作者：Kinugasa H1, Ikeda F, Takaguchi K, Mori C, Matsubara T, Shiraha H, Takaki A, Iwasaki Y, Toyooka S, Yamamoto K.

网址:PMID: 26115551

求助者：czh

• 求助时间：2015/6/28 23:38:38
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• 文献摘要：

BACKGROUND: The efficacy of a direct-acting antiviral agent (DAA) is compromised by the development of drug resistance. The associations between resistance-associated virus (RAV) and therapeutic outcomes have not been well-understood. METHODS: Thirty patients with HCV genotype 1b were enrolled, and treated for 24 weeks with asunaprevir (ASV) and daclatasvir (DCV). Viral sequences in non-structural (NS) regions 3 and 5A in serum and liver tissue before treatment were examined with direct sequencing, Next-generation sequencing (NGS), and the PCR-invader method to evaluate the importance of drug-resistance in the prediction of the outcomes of ASV plus DCV therapy. RESULTS: Of 30 patients (17 naïve patients, 5 interferon-intolerant patient, and 8 non-responders), 25 patients (83.3%) achieved sustained virological response (SVR) 24 weeks after the treatment. Viral breakthrough occurred in 3 naïve patients and one non-responder. One naïve patient experienced viral relapse. Among 25 patients without RAV, 24 obtained SVR, whereas 5 patients had RAV with a 1.3 to 88% frequency, resulting in various therapeutic outcomes. As for HCV compartments, similar RAVs were detected in serum and liver tissue for a patient obtaining SVR despite HCV NS5A Y93H and another developed viral breakthrough although no RAV was detected. Direct sequencing could not detect RAVs in low frequency (1.3 to 12%) for 3 of 4 patients. CONCLUSIONS: Low frequency of RAVs might not affect the outcomes of ASV plus DCV therapy. Deep sequencing and PCR-invader methods can detect clinically significant RAVs for ASV plus DCV therapy.

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