No One Size Fits All—Shortening Duration of Therapy With Direct-Acting Antivirals for Hepatitis C Genotype 1 Infection

O. El Sherif; N. Afhdal; M. Curry


J Viral Hepat. 2017;24(10):808-813. 

In This Article

Abstract and Introduction


The advent of shorter duration, highly effective and well-tolerated interferon-free therapy now provides an opportunity for virtually all HCV-infected individuals to be cured. However, there continues to be a need to simplify and shorten treatment duration. Shortening therapy to 8 weeks with sofosbuvir and ledipasvir can be considered in treatment patients with HCV genotype 1 infection and low baseline viral load. A number of other 8-week dual and triple therapy direct-acting antiviral (DAA) regimens are in advanced clinical development. Several small studies have further demonstrated the feasibility of 6 weeks of sofosbuvir therapy in combination with an NS5A inhibitor and a protease inhibitor for HCV genotype 1. Four weeks of therapy with various combinations of the currently available DAAs appears to be suboptimal with poor response rates observed in phase 2 trials. Response-guided therapy is another promising tool that may allow for shorter therapy but require further research. Shortening therapy and retreating relapsers may be a viable cost-saving measure, but requires further cost-benefit analysis and more data on the impact of resistance on retreatment options.


Hepatitis C virus (HCV) infection remains a major global public health problem. Despite the declining number of new infections in the developed world, the health care and societal burden of advanced liver disease related to HCV is expected to increase over the next decade.[1] Historically, treatment with interferon (IFN) was poorly tolerated and associated with long treatment durations between 24 and 48 weeks.[2] The advent of shorter duration, highly effective and well-tolerated interferon-free therapy now provides an opportunity for virtually all HCV-infected individuals to be cured.[3–12] There continues to be a need to simplify therapy and shorten treatment duration while maintaining high cure rates to expand treatment access.

The rapidity of viral suppression seen with two or more direct-acting antivirals in combination has allowed for shorter duration of HCV therapy compared to interferon-containing regimens. Three interferon-free direct-acting antiviral (DAA) regimens for the treatment of hepatitis C genotype 1 infection have been approved in the United States and Europe since 2014. Sofosbuvir and ledipasvir are licensed for 12 or 24 weeks. Additionally, this regimen is optional for 8 weeks of therapy in noncirrhotic treatment-naïve patients with a low viral load. The triple therapy combination of ritonavir-boosted paritaprevir, ombitasvir and dasabuvir is approved for 12 or 24 weeks. The fixed-dose combination of grazoprevir and elbasvir is approved for 12 or 16 weeks. These approvals were supported by extensive and robust phase 3 clinical trial programmes.[3–12]

These clinical trial programmes were designed with the goal of maximizing the SVR rates across the overall treated population. As a result, some patients received longer therapy than they may have required, and 12 weeks of therapy may represent overtreatment for a proportion of patients. Shortening therapy has several potential advantages. Shorter therapy will reduce the cost of treatment, allowing more patients to access therapy, especially in the current environment of pricing per pill.

We review the available data on the treatment of hepatitis C therapy genotype 1 mono-infection for <12 weeks, including efficacy, resistance, compliance and cost-effectiveness.