Sofosbuvir 200mg tablets

IntroductionDirect antiviral agents (DAAs) have dramatically changed the landscape of liver diseases associated with chronic hepatitis C virus (HCV) infection. However, limited data are available on the antiviral effect of sofosbuvir (SOF) + velpatasvir (VEL) ± ribavirin (RBV), SOF + VEL + voxilaprevir (VOX), and glecaprevir (GLE) + pibrentasvir (PIB) in treating patients infected with HCV GT3 in a real-world setting.MethodsUsing the EMBASE, PubMed, and Cochrane Library databases, articles were screened from 1 January 2016 to 1 June 2024. The sustained virologic response (SVR) rates were analyzed using the Freeman–Tukey double arcsine transformation in a random-effects model in R4.1.0 software.ResultsWe recruited 3,177 patients with HCV GT3 in 19 studies from 9 countries. The pooled SVR12/24 rate of the three evaluated regimens was 94.00% (95% CI: 90.87-96.59%). Furthermore, the SVR rate was 83.81% (95% CI: 75.70-90.62%) in patients receiving SOF+VEL+VOX; 94.98% (95% CI: 92.02-97.33%) in patients receiving SOF+VEL ± RBV; and 96.96% (95% CI: 93.20-99.45%) in patients receiving GLE+PIB. The pooled SVR12/24 rate of the three regimens was 95.70% (95% CI: 91.74-98.58%) and 90.50% (95% CI: 83.50-95.90%) in non-cirrhotic and cirrhotic patients, respectively. The pooled SVR rate was 96.79% (95% CI: 93.37-99.13%) and 88.41% (95% CI: 82.67-93.22%) in treatment-naive and treatment-experienced patients, respectively.ConclusionSOF+VEL ± RBV, GLE+PIB, and SOF+VEL+VOX had good antiviral effectiveness for chronic HCV-GT3 infection in real-world settings. Factors such as cirrhosis and treatment experience, especially previous DAA treatment failure, may influence the SVR rate.

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BackgroundWHO recommends treating hepatitis C infection with one of three antiviral combinations for 8-12 weeks. No randomised trials have compared these regimens, and high cure rates might be achievable with shorter durations of therapy. We aimed to compare sofosbuvir-daclatasvir with sofosbuvir-velpatasvir, and to evaluate potential novel treatment strategies.MethodsWe conducted a multi-arm, open-label, randomised controlled non-inferiority trial in two public hospitals in Viet Nam. Adults (aged ≥18 years) with chronic hepatitis C infection and mild-to-moderate liver fibrosis were eligible. Recruitment was stratified by centre and viral genotype (1-5 vs 6) with 1:1 random allocation to an oral fixed-dose combination of sofosbuvir 400 mg plus daclatasvir 60 mg (sofosbuvir-daclatasvir) or sofosbuvir 400 mg plus velpatasvir 100 mg (sofosbuvir-velpatasvir). Participants were simultaneously factorially randomly assigned to one of four treatment strategies: 12 weeks' standard of care (SOC); 4 weeks' therapy with four weekly PEGylated interferon alfa-2a subcutaneous injections; induction and maintenance therapy with 2 weeks' standard therapy followed by 10 weeks' therapy 5 days a week; and response-guided therapy (RGT) for 4, 8, or 12 weeks determined by viral load on day 7. The primary outcome was sustained virological response (SVR) 12 weeks after treatment completion, analysed in all evaluable participants regardless of actual treatment received. We chose a 5% non-inferiority margin for the drug comparison, and a 10% non-inferiority margin for the treatment strategy comparisons. Safety was assessed in all randomised participants. This trial is registered with ISRCTN, 61522291, and is completed.FindingsBetween June 19, 2020, and May 10, 2023, 624 participants were randomised (470 [75%] were male and 154 [25%] were female). 296 (47%) had genotype 6 and 328 (53%) had genotypes 1-5. The primary outcome was assessable in 609 (98%) participants. SVR occurred in 294 (97%) of 302 participants in the sofosbuvir-daclatasvir group and 292 (95%) of 307 participants in the sofosbuvir-velpatasvir group (risk difference 2·2%, 90% credible interval [CrI] -0·2 to 4·8, within the 5% non-inferiority margin; 93% probability that sofosbuvir-daclatasvir is superior to sofosbuvir-velpatasvir). SVR occurred in 148 (99%) of 150 in the SOC group, 143 (94%) of 152 in the 4-week antiviral plus interferon group (-4·5%, 90% CrI -8·3 to -1·3), 151 (99%) of 152 in the induction-maintenance group (0·6%, -1·1 to 2·7), and 144 (93%) of 155 in the RGT group (-5·7%, -9·6 to -2·3); all risk differences were within the 10% non-inferiority margin. Serious adverse events were rare (11 [4%] of 313 participants in the sofosbuvir-velpatasvir group vs six [2%] of 311 in the sofosbuvir-daclatasvir group; risk difference -1·6% [95% CrI -4·2 to 0·8]) with no evidence of differences between regimens or strategies, but adverse reactions were very common in the 4-week antiviral plus interferon group compared with the other treatment strategies (risk difference vs SOC group, 66·8% [59·2 to 74·0]; pInterpretationSofosbuvir-daclatasvir was non-inferior to sofosbuvir-velpatasvir. High efficacy was seen with novel strategies, which might help to inform approaches to treatment for harder-to-reach populations.FundingWellcome Trust.

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Background: The coronavirus disease 2019 (COVID-19) pandemic has engendered scores of deaths worldwide. Just as the development of varying procedures during the pandemic has helped inhibit the disease, none is considered a definitive treatment protocol for this problem, as each induces some clinical complications pertinent to the disease. This study thus assessed the early use of sofosbuvir in outpatients with mild COVID-19. Materials and Methods: This randomized clinical trial study was conducted on 360 patients with mild COVID-19 infection at 17 Shahrivar Ahvaz Health Center. These patients were randomly divided into the intervention and control groups. Both the control and intervention groups received 400 mg of sofosbuvir and a placebo for seven days, respectively. After 14 days from the onset of the treatment, the duration of symptoms, the necessity of hospitalization, the mean of hospitalization duration, and mortality were assessed.Results: The most common symptoms in the intervention and control groups were coughs with a frequency of 46 (25.6%) and 54(30%), respectively.The two groups showed no statistically significant difference in the frequency of the first observed clinical symptom related to the disease (P=0.2). The mean days that the patients were symptomatic in the control group were 14±4.17, whereas, in the intervention group, it was 12.12±3.15 (P=0.08). The frequency of hospitalization in the control and intervention groups was 7 (3.8%) and 4 (2.22%), respectively (P=0.11). Moreover, the mean days of hospitalization in the control and the intervention groups were 4±1.1 and 3±0.8, respectively (P=0.15). In addition, the two groups had a similar frequency of hospitalization in the ICU (0) and mortality rate (0). Conclusion: Sofosbuvir alone cannot play a significant role in the treatment of outpatients with mild COVID-19.

Abstract licence: CC BY 4.0

Background & aimsWe evaluated impact of hepatitis C treatment adherence support among people who inject drugs (PWID) in India using a precision trial design.MethodsTreatment naïve participants with a history of drug injection were recruited from community-based clinics across 7 cities. All received sofosbuvir/velpatasvir once/day for 12 weeks. Failure risk was defined a priori using a prognostic score including age, sex, income, homelessness, injection frequency, depressive symptoms, quality of life indicators and sexual partners. Elevated risk were randomized 3:2:1 to high (patient navigation [PN]+flexible directly observed therapy [≥1 dose/week observed]), medium (PN contact ≥every 2 weeks) or low intensity support. Minimal risk were randomized 1:2:3 to high, medium and low intensity support. Primary outcome was sustained virologic response (SVR; HCV RNA Results3000 were randomized (1/2021-12/2022; 2048 minimal, 952 elevated risk), 2798 (93.3%) completed SVR assessment. In minimal risk participants, SVR was 62.6%, 60.8% and 68.3% in low, medium and high intensity support, respectively. In elevated risk participants, SVR was 48.4%, 45.5% and 50.8%. 51 experienced a serious adverse event (35 deaths). In minimal risk participants, we observed superiority of high intensity (adjusted relative risk vs. low [aRR] 1.09; 95% confidence interval [CI]: 1.00-1.19; p=0.04) not medium intensity (aRR 0.97; 95% CI: 0.90-1.05) support. In elevated risk participants, there was no impact (low vs. high 0.96; 95% CI: 0.80-1.15; medium vs. high 0.89; 95% CI: 0.77-1.04). Every 10% decrease in prognostic score was associated with 1.06 increase in SVR (95% CI: 1.04-1.08).ConclusionsPrognostic scores could help target interventions more efficiently; greater adherence support and/or novel interventions are needed to improve SVR for the highest risk.Clinical trial numberClinicalTrials.gov NCT04652804.Impact and implicationsThis trial represents one of the largest trials to date of hepatitis C treatment. Our results, which demonstrate limited impact of adherence support interventions and sub-optimal sustained virologic response (SVR) among community-based people who inject drugs (PWID), suggest that more intensive or different tools and or strategies will be needed to support HCV elimination in populations like PWID. At the same time, these results provide strong evidence for the use of prognostic scores in trials as well as potentially in the delivery of interventions particularly when resources are scarce.

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ObjectiveTo determine whether an 8-week regimen of sofosbuvir/ravidasvir is non-inferior to the standard 12-week regimen in non-cirrhotic chronic hepatitis C virus (HCV) infection.Design or methodsWe conducted a multicenter open-label, randomized, non-inferiority clinical trial across nine hospitals and 17 primary healthcare centers in Malaysia. Adults aged 18-69 years with chronic HCV infection without cirrhosis were randomized (1:1) to receive 8 or 12 weeks of sofosbuvir/ravidasvir. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). The non-inferiority margin was 5%. The primary analysis was performed in the modified intention-to-treat population, excluding participants with missing primary endpoint data.ResultsBetween March 2021, and March 2023, 322 participants were randomized (161 per arm). Among those with available SVR12 results, 142/152 (93.4%) in the 8-week group and 143/153 (93.5%) in the 12-week group (difference: -0.04%; 90% CI: -4.94% to 4.85%; P = 0.047), demonstrating non-inferiority. Efficacy was consistent across genotype, baseline viral load, and HIV co-infection subgroups. Treatment-emergent adverse events were comparable and predominantly mild; no treatment-related serious adverse events occurred.ConclusionAn 8-week sofosbuvir/ravidasvir regimen achieved SVR12 comparable to 12 weeks in non-cirrhotic adults with chronic HCV infection and was well tolerated. Further pragmatic and cost-effectiveness studies are needed to inform large-scale implementation.Trial registrationClinicalTrials.gov Identifier: NCT04885855 [09/05/2021].

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