Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Public Health Laboratory, Alberta Precision Laboratories, Edmonton, AB, Canada.
J Clin Virol. 2023 May;162:105445. doi: 10.1016/j.jcv.2023.105445. Epub 2023 Apr 6.
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.
人类杯状病毒（HPgV）是一种单链 RNA 病毒，与丙型肝炎病毒（HCV）密切相关。HPgV 也已被证明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都有关联。目前尚无针对 HPgV 的既定治疗方法。
估计在接受直接作用抗病毒药物（DAA）治疗 HCV 的 HCV/HIV 合并感染患者队列中 HPgV 的流行率，并研究 DAA 治疗对 HPgV 感染的影响。
从 DAA 治疗前、治疗中和治疗后采集的血浆样本中提取 RNA。通过针对 NS5A 和 5'UTR 结构域的液滴数字 PCR 检测定量 HPgV RNA 丰度，并通过 RT-qPCR 进行验证。分析临床、人口统计学和治疗数据。
在开始 DAA 之前，100 名患者的血浆中有 26 名（26%）检测到并定量了 HPgV RNA。检测到 HPgV 的患者更可能是男性，HIV 血浆峰值水平更高，并有注射吸毒史。接受索非布韦/雷迪帕韦（n=9）的患者在 DAA 完成时的 HPgV 水平显著降低，并且在 DAA 完成后的 HPgV 反弹水平也低于接受索非布韦/维帕他韦（n=11）的患者，尽管两种方案都能显著降低 DAA 完成后病毒血症。接受聚乙二醇干扰素的患者（n=2）也观察到 HPgV 的持续抑制。
在 HCV/HIV 合并感染患者中经常检测到 HPgV RNA，DAA 和聚乙二醇干扰素治疗可抑制 HPgV，其中索非布韦/雷迪帕韦显示出最大的抗病毒活性。这些发现为 HPgV 感染提供了潜在的治疗策略。
