ledipasvir and Viremia

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​.

Topics: Antiviral Agents; Coinfection; Female; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; HIV; HIV Infections; Humans; Interferons; Male; Pegivirus; Polyethylene Glycols; RNA, Viral; Sofosbuvir; Viremia

Hepatitis B reactivation in patients with resolved HBV can occur during hepatitis C treatment with direct-acting antivirals, but only a few cases have been described. It is not clear which patients are at risk for HBV reactivation and how to manage them.. Three patients (all hepatitis B surface antigen [HBsAg]-negative, antibody to hepatitis B core [anti-HBc] positive and HBV DNA negative) experienced a late HBV reactivation 12 weeks post-treatment but were able to control their viraemia. HCV RNA, HBV DNA, anti-HBc and anti-HBs were measured in these patients and in 37 HBsAg-negative, anti-HBc positive, HBV DNA negative control patients during direct-acting antiviral therapy for chronic hepatitis C.. Baseline anti-HBs do not differ between patients with and without HBV reactivation. Patients with HBV reactivation, however, significantly increased their anti-HBs at time of reactivation, while patients without HBV reactivation show stable anti-HBs during therapy (P=0.007).. Anti-HBs might be an important marker to delineate patients at risk for clinically significant HBV reactivation.

Topics: Antiviral Agents; Benzimidazoles; DNA, Viral; Female; Fluorenes; Hepacivirus; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Core Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis C, Chronic; Humans; Male; Middle Aged; Prospective Studies; Sofosbuvir; Viremia; Virus Activation