Abstract：
Human pegivirus (HPgV) is a single-stranded RNA virus that is closely related to hepatitis C virus (HCV). HPgV has also been shown to infect patients with human immunodeficiency virus (HIV). The mechanisms and disease outcomes of HPgV infections are largely unknown, although it has been implicated in both cancer and neurological diseases. There are no established therapies for HPgV.
To estimate the prevalence of HPgV in a cohort of HCV/HIV co-infected patients undergoing treatment for HCV with direct acting antivirals (DAA) and investigate the effect of DAA therapy on HPgV infection.
RNA was extracted from plasma samples collected at time points before, during, and after DAA. HPgV RNA abundance was quantified by droplet digital PCR assays targeting the NS5A and 5\'UTR domains and confirmed by RT-qPCR. Clinical, demographic and treatment data were analysed.
HPgV RNA was detected and quantified in 26 of 100 patients\' plasma (26%) before starting DAA. Patients with detectable HPgV were more likely to be male, had higher peak HIV plasma levels, and a history of injection drug use. Patients receiving sofosbuvir/ledipasvir (n = 9) displayed significantly lower HPgV levels at time of DAA completion and had lower post-DAA HPgV rebound levels compared to patients receiving sofosbuvir/velpatasvir (n = 11) although both regimens significantly reduced viremia directly following DAA completion. Sustained suppression of HPgV was also observed among patients (n = 2) receiving pegylated-interferon.
HPgV RNA was frequently detected in HCV/HIV co-infected patients and was supressed by DAA and pegylated interferon therapies with sofosbuvir-ledipasvir showing greatest antiviral activity. These findings suggest potential treatment strategies for HPgV infections.
To estimate the prevalence of HPgV in a cohort of HCV/HIV co-infected patients undergoing treatment for HCV with direct acting antivirals (DAA) and investigate the effect of DAA therapy on HPgV infection.
RNA was extracted from plasma samples collected at time points before, during, and after DAA. HPgV RNA abundance was quantified by droplet digital PCR assays targeting the NS5A and 5\'UTR domains and confirmed by RT-qPCR. Clinical, demographic and treatment data were analysed.
HPgV RNA was detected and quantified in 26 of 100 patients\' plasma (26%) before starting DAA. Patients with detectable HPgV were more likely to be male, had higher peak HIV plasma levels, and a history of injection drug use. Patients receiving sofosbuvir/ledipasvir (n = 9) displayed significantly lower HPgV levels at time of DAA completion and had lower post-DAA HPgV rebound levels compared to patients receiving sofosbuvir/velpatasvir (n = 11) although both regimens significantly reduced viremia directly following DAA completion. Sustained suppression of HPgV was also observed among patients (n = 2) receiving pegylated-interferon.
HPgV RNA was frequently detected in HCV/HIV co-infected patients and was supressed by DAA and pegylated interferon therapies with sofosbuvir-ledipasvir showing greatest antiviral activity. These findings suggest potential treatment strategies for HPgV infections.
摘要：
背景：人类pegivirus（HPgV）是一种与丙型肝炎病毒（HCV）密切相关的单链RNA病毒。HPgV也已显示感染人类免疫缺陷病毒(HIV)的患者。HPgV感染的机制和疾病结果在很大程度上是未知的，尽管它与癌症和神经系统疾病有关。没有确定的HPgV治疗方法。
目的：评估接受直接抗病毒药物（DAA）治疗的HCV/HIV共感染患者队列中HPgV的患病率，并研究DAA治疗对HPgV感染的影响。
方法：从之前时间点收集的血浆样品中提取RNA，during,在DAA之后。通过靶向NS5A和5'UTR结构域的液滴数字PCR测定定量HPgVRNA丰度，并通过RT-qPCR确认。临床,分析了人口统计学和治疗数据.
结果：在开始DAA之前，在100名患者中的26名（26％）血浆中检测并定量了HPgVRNA。检测到HPgV的患者更可能是男性，有更高的艾滋病毒血浆峰值水平，以及注射药物使用史.与接受sofosbuvir/velpatasvir（n=11）的患者相比，接受sofosbuvir/ledipasvir（n=9）的患者在DAA完成时显示出显着降低的HPgV水平，并且DAA后HPgV反弹水平较低，尽管两种方案都显着降低了DAA完成后的病毒血症。在接受聚乙二醇干扰素的患者（n=2）中也观察到HPgV的持续抑制。
结论：在HCV/HIV共感染的患者中经常检测到HPgVRNA，DAA和聚乙二醇化干扰素治疗与sofosbuvir-ledipasvir表现出最大的抗病毒活性。这些发现表明了HPgV感染的潜在治疗策略。
目的：评估接受直接抗病毒药物（DAA）治疗的HCV/HIV共感染患者队列中HPgV的患病率，并研究DAA治疗对HPgV感染的影响。
方法：从之前时间点收集的血浆样品中提取RNA，during,在DAA之后。通过靶向NS5A和5'UTR结构域的液滴数字PCR测定定量HPgVRNA丰度，并通过RT-qPCR确认。临床,分析了人口统计学和治疗数据.
结果：在开始DAA之前，在100名患者中的26名（26％）血浆中检测并定量了HPgVRNA。检测到HPgV的患者更可能是男性，有更高的艾滋病毒血浆峰值水平，以及注射药物使用史.与接受sofosbuvir/velpatasvir（n=11）的患者相比，接受sofosbuvir/ledipasvir（n=9）的患者在DAA完成时显示出显着降低的HPgV水平，并且DAA后HPgV反弹水平较低，尽管两种方案都显着降低了DAA完成后的病毒血症。在接受聚乙二醇干扰素的患者（n=2）中也观察到HPgV的持续抑制。
结论：在HCV/HIV共感染的患者中经常检测到HPgVRNA，DAA和聚乙二醇化干扰素治疗与sofosbuvir-ledipasvir表现出最大的抗病毒活性。这些发现表明了HPgV感染的潜在治疗策略。
