与人类pegivirus1(HPgV-1)的共感染在慢性丙型肝炎病毒(HCV)患者中很常见。然而,关于在HCV治疗期间HPgV-1是否受到直接作用的抗病毒药物的影响知之甚少.对来自88个选择的接受药物治疗的慢性HCV患者的血浆的RNA进行宏基因组分析和逆转录酶定量PCR(RT-qPCR)。这些HCV患者中有20名(23%)患有HPgV-1共感染,在治疗和随访期间进行RT-qPCR以研究HPgV-1RNA滴度。回收的序列可以组装成完整的HPgV-1基因组,大多数形成了基因型2亚进化枝。所有HPgV-1病毒基因组区域均处于阴性纯化选择下。5例患者的Glecaprevir/pibrentasvir治疗并未持续降低HPgV-1的基因组滴度。相比之下,一个log10下降的HPgV-1滴度在第2周观察到10例患者治疗期间含索非布韦方案,持续到治疗结束(EOT),在两种情况下降低到低于测定的检测限。对于5例接受ledipasvir/sofosbuvir治疗的患者,包括聚乙二醇干扰素,滴度在第2周时下降至检测限以下,并且EOT仍无法检测到。随后,所有患者的HPgV-1滴度回升至治疗前水平.总之,我们发现,包括聚合酶抑制剂索非布韦的HCV治疗方案导致HPgV-1滴度降低,聚乙二醇干扰素的加入增加了对合并感染患者的影响。这表明蛋白酶和NS5A抑制剂对HCV的高特异性和索非布韦,尤其是聚乙二醇化干扰素的更广谱活性。
目的:人类pegivirus1合并感染在丙型肝炎病毒(HCV)患者中很常见,坚持多年。然而,对于针对HCV的全基因型直接作用抗病毒药物(DAA)治疗如何影响pegivirus合并感染,知之甚少。我们通过对接受蛋白酶的慢性HCV患者的宏基因组分析鉴定了人类pegivirus,NS5A,和聚合酶抑制剂治疗,在一些添加聚乙二醇干扰素的患者中,并跟踪两种病毒的病毒动力学以研究治疗效果。只有在包括更广谱药物索非布韦的HCVDAA治疗方案中,我们才能检测到pegivirus滴度的持续下降,然而,治疗停止后反弹至预处理水平。聚乙二醇化干扰素的加入给出了最高的效果与聚乙二醇病毒滴度降低到低于测定检测极限,但没有许可。这些结果表明,一线HCV药物对最密切相关的人类病毒的作用有限,但是sofosbuvir似乎有可能被用于其他病毒性疾病。
Coinfections with human
pegivirus 1 (HPgV-1) are common in chronic hepatitis C virus (HCV) patients. However, little is known about whether HPgV-1 is affected by direct-acting antivirals during HCV treatment. Metagenomic analysis and reverse transcriptase-quantitative PCR (RT-qPCR) were performed on RNA from the plasma of 88 selected chronic HCV patients undergoing medical treatment. Twenty (23%) of these HCV patients had HPgV-1 coinfections and were followed by RT-qPCR during treatment and follow-up to investigate HPgV-1 RNA titers. Recovered sequences could be assembled to complete HPgV-1 genomes, and most formed a genotype 2 subclade. All HPgV-1 viral genomic regions were under negative purifying selection. Glecaprevir/pibrentasvir treatment in five patients did not consistently lower the genome titers of HPgV-1. In contrast, a one log10 drop of HPgV-1 titers at week 2 was observed in 10 patients during treatment with sofosbuvir-containing regimens, sustained to the end of treatment (EOT) and in two cases decreasing to below the detection limit of the assay. For the five patients treated with ledipasvir/sofosbuvir with the inclusion of pegylated interferon, titers decreased to below the detection limit at week 2 and remained undetectable to EOT. Subsequently, the HPgV-1 titer rebounded to pretreatment levels for all patients. In conclusion, we found that HCV treatment regimens that included the polymerase inhibitor sofosbuvir resulted in decreases in HPgV-1 titers, and the addition of pegylated interferon increased the effect on patients with coinfections. This points to the high specificity of protease and NS5A inhibitors toward HCV and the more broad-spectrum activity of sofosbuvir and especially pegylated interferon.
OBJECTIVE: Human
pegivirus 1 coinfections are common in hepatitis C virus (HCV) patients, persisting for years. However, little is known about how
pegivirus coinfections are affected by treatment with pangenotypic direct-acting antivirals (DAAs) against HCV. We identified human
pegivirus by metagenomic analysis of chronic HCV patients undergoing protease, NS5A, and polymerase inhibitor treatment, in some patients with the addition of pegylated interferon, and followed viral kinetics of both viruses to investigate treatment effects. Only during HCV DAA treatment regimens that included the more broad-spectrum drug sofosbuvir could we detect a consistent decline in pegivirus titers that, however, rebounded to pretreatment levels after treatment cessation. The addition of pegylated interferon gave the highest effect with
pegivirus titers decreasing to below the assay detection limit, but without clearance. These results reveal the limited effect of frontline HCV drugs on the closest related human virus, but sofosbuvir appeared to have the potential to be repurposed for other viral diseases.