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ObjectiveTo investigate the efficacy and safety of sofosbuvir/velpatasvir alone or in combination with ribavirin in Chinese patients with genotype 3B HCV/HIV infection. MethodsA total of 299 patients with genotype 3B HCV/HIV infection who attended The Third People’s Hospital of Kunming from January 2017 to December 2020 were enrolled and treated with sofosbuvir/velpatasvir alone or in combination with ribavirin for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The patients were evaluated in terms of sustained virologic response at 12 weeks after treatment （SVR12） and adverse reactions. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the Agresti-Coull method was used to evaluate the 95% confidence interval （CI） of SVR12； univariate and multivariate non-conditional logistic regression analyses were used to investigate the influencing factors for SVR. ResultsThe 299 patients with genotype 3B HCV/HIV infection had a mean age of 43.92±6.84 years， among whom the male patients accounted for 77.3% （231/299）， the patients with liver cirrhosis accounted for 36.5% （109/299）， the patients with a history of antiviral therapy accounted for 13.4% （40/299）， and the patients receiving sofosbuvir/velpatasvir combined with ribavirin accounted for 27.8% （83/299）. The overall SVR was 87.0% （260/299） for all patients， and there was no significant difference in SVR12 between the patients receiving sofosbuvir/velpatasvir alone and those receiving sofosbuvir/velpatasvir combined with ribavirin （87.5% vs 85.5%， χ2=0.203， P=0.653）. There was a significant difference in SVR12 between the patients without liver cirrhosis and those with liver cirrhosis （90.0% vs 81.7%， χ2=4.256， P=0.039）， and the patients receiving antiviral therapy for the first time had a significantly higher SVR12 than the treatment-experienced patients （93.4% vs 45.0%， χ2=71.670， P<0.001）. The univariate and multivariate logistic regression analyses showed that platelet count （odds ratio ［OR］=0.957， 95%CI： 0.931 — 0.984， P=0.002）， liver stiffness measurement （OR=1.446， 95%CI： 1.147 — 1.822， P=0.002）， and experience in treatment （OR=13.807， 95%CI： 2.970 — 64.174， P=0.001） were independent influencing factors for SVR in patients with genotype 3B HCV/HIV infection. There were 41 cases of serious adverse events， all of which occurred within 2 weeks after antiviral therapy， and 28 cases were resolved without drug withdrawal or active treatment， while 13 cases were not resolved after active treatment and were resolved after the antiviral drugs were stopped for 2 — 5 days， with no similar reactions observed when the drugs were used again after remission. ConclusionSofosbuvir/velpatasvir alone or in combination with ribavirin has relatively good efficacy and safety in patients with genotype 3B HCV/HIV infection.
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Objective:To explore the efficacy and safety of sofosbuvir-based direct-acting antiviral treatment in children and adolescent patients with chronic hepatitis C (CHC).Methods:A total of 52 children and adolescent patients who admitted to The Third People′s Hospital of Kunming City and The People′s Hospital of Fuyuan County aged from three to 17 years old with CHC from January 2018 to August 2022 were enrolled, and their basic information was collected. Patients were treated with sofosbuvir/velpatasvir (SOF/VEL) or ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin for 12 weeks. The biochemical and virological indexes were followed up before and after treatment and 12 weeks after withdrawal. The primary endpoint was the sustained virological response (SVR) at week 12 of follow-up after treatment, and the occurrence of adverse events (AE) during treatment. Statistical analysis was used by nonparametric test.Results:A total of 52 patients with CHC including 38 children and 14 adolescents were enrolled. Thirty-one were male and 21 were female. The age was 9(7, 12) years old. Among 52 patients, seven patients were type 1b, 11 were type 2a, three were type 2, five were type 3a, 18 were type 3b, one was type 6a, three were type 6k, four were type 6n and one was type 6v. Twelve (23.1%) patients were vertical transmission, 21(40.4%) patients had horizontal transmission among family members, two (3.8%) patients were blood fluid transmission, and 17(32.7%) were unknown transmission route. Compared with the baseline levels, Total bilirubin, alanine aminotransferase and aspartate aminotransferase were all significantly decreased after 12 weeks of treatment and 12 weeks after withdrawal, and the differences were statistically significant ( F=12.71, 30.23 and 42.52, respectively, all P<0.05). Up to September 30, 2022, 100.0%(52/52) of patients achieved SVR at the end of treatment. For patients who completed follow-up for 12 weeks after treatment, 95.8%(46/48) achieved SVR. Common AEs during treatment were fatigue (11.5%(6/52)), headache (5.8%(3/52)), dizziness (1.9%(1/52)), abdominal pain (3.8%(2/52)), diarrhea (1.9%(1/52)), rash (1.9%(1/52)) and skin pruritus (1.9%(1/52)). No patients discontinued treatment because of AE. Conclusions:Sofosbuvir-based direct-acting antiviral treatment is efficient and well-tolerated in children and adolescent patients with CHC. No patients discontinued treatment due to AE.
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ABSTRACT Despite the high sustained virologic response (SVR) rates of direct-acting antiviral (DAAs) therapy, a small number of patients does not eradicate the virus, and these patients represent a challenge. This study aims to compare the outcomes of three second-line regimens for DAAs-experienced patients with chronic hepatitis C (CHC). This prospective observational study was conducted at the Damanhur Viral Hepatitis Center from January 2017 to February 2020. We included patients with CHC who did not achieve SVR after the complete course of Sofosbuvir/Daclatasvir±Ribavirin (SOF/DAC±RBV). The primary endpoint was SVR-12 after re-treatment. This study included 360 patients (with a mean age of 51.53±11.38 years). Approximately 51.1% of the patients were males, and 65.5% had liver cirrhosis. All patients of group 1 (45 patients) received SOF/VEL/VOX over 12-weeks; SVR-12 was achieved in 44 patients (97.8%). Group 2 (28 patients) received SOF/DAC/RBV over 24-weeks; (one patient was lost during follow-ups and one patient discontinued treatment due to hepatic decompensation). SVR-12 was achieved in 25 patients (96.2%). Group 3 (287 patients) received SOF/Ombitasvir/Paritaprevir/Ritonavir/RBV) over 12-weeks. Eight patients were lost during follow-ups, and one patient discontinued treatment due to grade 4 adverse events. SVR-12 was achieved in 276 patients (99.3%). There was no difference between the groups regarding their age, gender distribution, baseline viral load or comorbidities. Adverse events (thrombocytopenia, anemia, hyperbilirubinaemia and prolonged INR) were significantly higher in group 3, while group 1 did not experience any. The three studied retreatment regimens can be used for DAAs treatment-experienced patients considering availability. The SOF/VEL/VOX combination had the least adverse events.
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The discovery of new direct-acting antiviral drugs gave rise to a leap forward in the treatment of hepatitis C viral infections. For the first time since 1998, the Food and Drug Administration (FDA) approved interferon-free oral treatment paradigms. Among the new treatment regimens, the combinations of Sofosbuvir and Velpatasvir became ideal treatment regimens for being potent, highly tolerated and used once daily. Hence an accurate, precise, selective and sensitive stability indicating method for simultaneous estimation of Sofosbuvir and Velpatasvir by High-Performance Thin Layer Chromatography has been developed and validated. Chromatographic separation was achieved on TLC plates coated with silica gel 60 F254 as stationary phase. Ethyl acetate: iso-propyl alcohol (9:1 v/v) was used as mobile phase.Densitometric scanning was carried out at 260 and 302 nm for Sofosbuvir and Velpatasvir, respectively. The method was successfully validated as per the ICH Guideline. The linear concentration range was100- 2000 ng/band (r2= 0.991) and 100-500 ng/band (r2 = 0.991) for SOF (Sofosbuvir) and VEL (Velpatasvir) respectively. The LOD were 25.16 ng/band and 9.96 ng/band for SOF and VEL, LOQ were 76.25 ng/band and 30.19 ng/band for SOF and VEL.The method could be applied to the quality control and routine analysis of Sofosbuvir and Velpatasvir in their pure forms and pharmaceutical formulations.
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Interferon-free direct-acting antiviral agent (DAA) therapy is preferred for the treatment of chronic hepatitis C (CHC) patients as it exhibits a higher rate of sustained virologic response (SVR), along with reduction in treatment related adverse drug reactions (ADR), which elevates the quality of life (QOL) of patients. The study aims to evaluate the healthrelated quality of life (HRQOL) in patients with CHC, receiving Daclatasvir or velpatasvir (DCV/VEL) therapy, using Short Form-36 (SF-36) as a tool. Methods: The study involves 50 CHC patients receiving DCV/VEL, who’s HRQOL was measured using SF-36. Laboratory investigational data and SVR was recorded, and SF-36 was filled by the patient at baseline (prior to therapy), week 12 (post initiation of therapy), end of treatment (EOT), and week 24 (post initiation of therapy. HRQOL were analyzed at week 24. The association between laboratory data and HRQOL was also evaluated. Results: In regard to HRQOL, statistically significant changes were observed in physical functioning, general health, and emotional role functioning in the period between baseline to week 12 and week 24, respectively. A considerable change was observed in laboratory parameters such as aminotranferases, platelet count, and Fibrosis-4 (Fib-4) index at each time point of study as compared to baseline. Conclusion: It was found that HRQOL of patients with CHC improved significantly along with hepatic functions during the clinical course of interferon-free DAA therapy (DCV/VEL).
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Velpatasvir is a new generation of NS5A inhibitors, and combined with marketed sofosbuvir, compound tablets Epclusa was obtained and approved by FDA in June, 2016, which is used for the treatment of adult patients infected with chronic hepatitis C vi-rus ( HCV) with all genotypes. The mechanism of action, pharmacodynamics, pharmacokinetics, clinical trials and safety of Epclusa were reviewed in this article.