Sofosbuvir and Ledipasvir in HIV/HCV Coinfected Pre and Post Liver Transplant

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Investigator: Peter G. Stock
Sponsor: NIH National Institute of Allergy and Infectious Disease

Location(s): United States

Description

The research plan will serve to address an important clinical challenge - how to insure that people with HCV/HIV coinfection attain pre- and post-transplant outcomes similar to those of HCV people without HIV. We propose an interventional study using novel DAAs, coupled with virologic and immunologic translational studies, to enhance our understanding of the factors responsible for sustained HCV viral eradication. The findings of this study are expected to transform the clinical management of HCV/HIV coinfected people with advanced liver disease, including transplant recipients.

The study will address a major barrier to progress in the field of transplantation in HCV/HIV coinfected subjects, namely the issue of severe HCV disease and aggressive recurrence following liver transplantation. Specifically, this will be a phase 2 study designed to evaluate the safety and efficacy of sofosbuvir/ledipasvir FDC tablet, for treatment duration of 12 weeks, in HCV/HIV coinfected subjects pre (n=25) or post (n=25) liver transplant. This novel and efficacious all oral DAA regimen is hypothesized to be safe, well-tolerated and yield higher rates of a sustained virologic response (SVR) compared to traditional interferon based therapy. Mechanistic studies will explore the impact of HIV coinfection on HCV viral kinetics and host-specific HCV immunity during therapy with FDC sofosbuvir/ledipasvir in the setting of cirrhosis and decompensated liver disease, and compare this to similar treatment in compensated cirrhosis or early liver disease. This information will be critical in designing future treatment algorithms to reduce treatment failures. Further mechanistic studies will evaluate the impact of medication induced immune suppression and HIV coinfection on HCV viral kinetic and peripheral HCV immunity during treatment with FDC sofosbuvir/ledipasvir in patients with recurrent HCV post- liver transplant. The generated data will allow us to infer the necessity of augmentation of immunity for HCV eradication in the setting of HIV coinfection and immunosuppression. The overarching goal of the research plan is straightforward; remove critical barriers to progress in liver transplantation of HCV/HIV coinfected people.