Real-World Efficacy and Safety of Pangenotypic Direct-Acting Antivirals Against Hepatitis C Virus Infection

Abstract

Background: Advances in the development of Direct-Acting Antivirals (DAAs), particularly pangenotypic drugs, have led to a high rate of hepatitis C virus (HCV) eradication. Notably, real- world studies have confirmed the efficacy and safety of pangenotypic DAA combinations reported in registration trials. The aim of this study was to review the treatment recommendations, and the efficacy and safety data of anti-HCV pangenotypic drugs reported in registration clinical trials and in recent real-life cohort studies. Methods: We reviewed the efficacy and safety data of pangenotypic anti-HCV drug combinations reported in original articles and in online conference abstracts. Results: Current pangenotypic drug combinations resulted in very high rates of sustained virologic response and few adverse reactions in real-life settings. SVR12 rates in real-life studies ranged from 90-100% depending on the pangenotypic combination, the HCV genotype and the stage of liver disease. Most adverse reactions reported in real-life settings were mild in intensity and rarely led to treatment discontinuation. These results are in accordance with those of clinical trials. Conclusion: Pangenotypic DAAs result in very high rates of sustained virologic responses and are well tolerated. However, they are contraindicated in patients with decompensated cirrhosis or advanced chronic kidney disease who failed previous DDA-based treatment. Further research is required to customize treatment to “unpackage” current DAA combinations and to develop generic drugs against HCV.

EASL recommendations on treatment of hepatitis C: Final update of the series☆

“…Generic drugs and their combinations produced by companies under the license of the Medicines Patent Pool and prequalified by WHO and/or other regulatory authorities have been shown to generate similar results to the original compounds, with similar safety and tolerability. [157][158][159][160][161][162][163][164][165][166][167] The panel recognises the heterogeneity of per capita incomes and health insurance systems across Europe and in other regions, and therefore the constraints that may necessitate continued utilisation of regimens described in previous versions of these recommendations but no longer recommended. In settings where none of the IFN-free, ribavirin-free options proposed in this document are available, options proposed in previous versions of these recommendations remain acceptable for patients likely to respond to these regimens until new DAAs become available and affordable; see prior EASL Recommendations on Treatment of Hepatitis C. 120,[168][169][170][171] In particular, in many lowand middle-income countries where the pangenotypic DAA combinations recommended in the present document are not available and/or not affordable, the combination of generic sofosbuvir and daclatasvir is safe and well tolerated and provides high SVR rates at a very low price.…”

Scaling up screening and treatment for elimination of hepatitis C among men who have sex with men in the era of HIV pre-exposure prophylaxis

“…S7ÀS12) were then validated against data suggesting a 55¢5% (95% CI 34¢4À72¢7%) decrease in the annual rate of new HIV infections among MSM over 2012À2017 in the UK [6]. HCV prevalence and incidence also decrease over this period due to an increase to DAA SVR rates from 2015 [35,36]. Despite being not fit to this data, our model projections for HCV incidence among HIV-diagnosed MSM and HIV-negative MSM off PrEP for 2012 are comparable to UK data estimates from that period, as shown in Supplementary Figs.…”

Prevalence and Clinical Significance of SEN-virus and TT- virus Infection in Chronic HCV Patients

“…Duration of therapy is 8-16 weeks depending on the stage of fibrosis, genotype, baseline viral load, prior treatment history and pre-existing resistance-associated variants. Most of these combinations have a high antiviral potency, fair tolerance and a reduced pill burden [21].…”