Safety, Tolerability, and Efficacy of Asunaprevir and Daclatasvir in Subjects Coinfected With HIV-HCV

Summary

Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the United States an estimated 4.1 million people are infected and HCV is the principal cause of death from liver disease and leading indication for liver transplantation. Within HIV/HCV co-infected patients, liver disease due to Hepatitis C progresses even more rapidly. While combination of ribavirin (RBV) and pegylated interferon (PEG) in combination with boceprevir/telaprevir is the currently recommended therapy for chronic HCV infection and has superior cure rates compared to PEG+RBV alone in HCV monoinfected patients, treatment is still associated with a high incidence of adverse events (AEs), discontinuations and poor cure rates in several populations. Within the HIV/HCV co-infected population treatment for HCV remains complicated given drug interactions between anti-retrovirals and HCV protease inhibitors, in addition to the extensive side-effects due to PEG +RBV alone. Recent studies have demonstrated that the use of a combination of anti-virals which target HCV without interferon (IFN) can cure HCV, without additional toxicities. These novel therapies that do not rely on an IFN backbone may additionally enhance cure rates in HIV/HCV co-infected, a population which has historically been difficult to cure. The findings from this study will aid in the understanding of antiviral and host responses and determinants of response to an IFN free regimen in HIV/HCV co-infected patients.

Timeline

Start

2014-02

Primary completion

2016-03

Completion

2016-11

Publications

• Background Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, Reindollar R, Rustgi V, McPhee F, Wind-Rotolo M, Persson A, Zhu K, Dimitrova DI, Eley T, Guo T, Grasela DM, Pasquinelli C. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012 Jan 19;366(3):216-24. doi: 10.1056/NEJMoa1104430.
• Background Zeuzem S, Buti M, Ferenci P, Sperl J, Horsmans Y, Cianciara J, Ibranyi E, Weiland O, Noviello S, Brass C, Albrecht J. Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. J Hepatol. 2006 Jan;44(1):97-103. doi: 10.1016/j.jhep.2005.10.003. Epub 2005 Nov 7.
• Background Kottilil S, Yan MY, Reitano KN, Zhang X, Lempicki R, Roby G, Daucher M, Yang J, Cortez KJ, Ghany M, Polis MA, Fauci AS. Human immunodeficiency virus and hepatitis C infections induce distinct immunologic imprints in peripheral mononuclear cells. Hepatology. 2009 Jul;50(1):34-45. doi: 10.1002/hep.23055.

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