Efficacy and Safety of Generic Sofosbuvir Plus Daclatasvir and Sofosbuvir/Velpatasvir in HCV Genotype 3-Infected Patients: Real-World Outcomes From Pakistan

Abstract

Background Direct-acting antivirals (DAAs) therapeutic regimens are highly effective against chronic hepatitis C virus (HCV) infection. However, HCV patients with genotype 3 (GT3) respond in a suboptimal way. This study aims to identify which of the DAAs-based therapeutic regimens are the best option for GT3. Methods Multiple governments and private tertiary care hospitals were involved in this real-life study of HCV-GT3 patients treated with DAAs. The efficacy and safety of generic sofosbuvir+daclatasvir±ribavirin (SOF+DCV±RBV) and sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) were assessed under the National Hepatitis C Program of Pakistan. Results Out of 1,388 participants, 70% of patients received SOF+DCV in government tertiary care hospitals and 30% received SOF/VEL in private tertiary care hospitals. The overall sustained virological responses (SVR) was 95.5%. The SVR rates at 12 weeks were comparable between SOF+DCV (94.4%) and SOF/VEL (94.7%) in chronic HCV patients. However, The SVR rates at 24 weeks were high in cirrhotic patients treated with SOF/VEL+RBV (88%) then SOF+DCV+RBV (83%). Non-responders were high in SOF-DCV than SOF-VEL (4.1 vs 3.8%, P = 0.05) regimen. In multivariate models, the significant predictors of non-SVR were age >60 years (odds ratio [OR] 4.46; 95% CI, 2.35–8.46, P = <0.001) and cirrhosis (OR 53.91; 95% CI, 26.49–109.6, P = <0.001). Skin rash (51 vs 44%) and oral ulcers (45 vs 40%) were high in patients receiving SOF-DCV then SOF-VEL. Conclusions Overall, the generic SOF+DCV ±RBV and SOF/VEL ± RBV achieved equally high SVR12 rates. However, SOF/VEL+RBV achieved a high SVR rate in cirrhotic patients then SOF+DCV+RBV. Old age and cirrhosis were significant predictors of reduced odds of SVR regardless of the regimen. Furthermore, the regimens were well tolerated in chronic HCV patients.

Efficacy and Safety of Sofosbuvir and Velpatasvir Combination for the Treatment of Chronic Hepatitis C in Patients With or Without Cirrhosis

“…Similarly, in a prospective observational study conducted in Pakistan in which 1,388 patients with chronic HCV were enrolled, and 30% of these patients received sofosbuvir and velpatasvir, the overall SVR rates for the cohort who received sofosbuvir and velpatasvir was 94.7, while in patients with cirrhosis, it was 88%. The findings of this study are in agreement with our study [ 12 ]. Our study showed relatively low SVR rates in patients with cirrhosis, 89.7% compared to 98.3% in non-cirrhotic chronic hepatitis C patients.…”

“…Our study showed relatively low SVR rates in patients with cirrhosis, 89.7% compared to 98.3% in non-cirrhotic chronic hepatitis C patients. Similar trends have been observed in other studies [ 11 , 12 ].…”

Effectiveness and Safety of Pangenotypic Regimens in the Most Difficult to Treat Population of Genotype 3 HCV Infected Cirrhotics

“…Mangia et al documented a 90.5% cure rate with SOF/VEL + RBV regimen in the RWE population, but only ten GT3 infected patients with liver cirrhosis were included [ 22 ]. The efficacy of 88% was demonstrated in a real-life population consisted of 34 patients, including 31 treatment-experienced with both IFN- and DAA-based except NS5A-containing regimens [ 23 ]. The much more numerous RWE cohort comprising 267 cirrhotic American Veterans treated with SOF/VEL + RBV analyzed by Belperio et al, including NS5A-experienced individuals, responded in 84.5% [ 20 ].…”

Hepatitis C virus: A critical approach to who really needs treatment

“…Three SOF-based treatments not only had SVR > 90% but their effects were equally fast in a series of patients with advanced fibrosis or cirrhosis[ 90 ]. Even low-priced generic DAAs were both clinically effective and cost-effective[ 91 , 92 ]. Similar efficacy between SOF/DCV and SOF/VEL in genotypes 2 and 3 was also reported in a real world study[ 93 ].…”