Hope for the eradication of HCV worldwide
Jean-François Delfraissy, French Agency for Research on AIDS and Viral Hepatitis, Institute of Microbiology and Infectious Diseases Internal Medicine, CHU Bicetre University, Paris 11, Paris, France
French Association for the study of the Liver
French National Agency for Drug and Health Products
French National Agency for Research on AIDS and viral hepatitis
French Temporary Authorization for Use
Direction Générale de Santé
Haute Autorité de Santé
hepatitis B virus
hepatitis C virus
human immunodeficiency virus
The mission of the ANRS (the French National Agency for Research on AIDS and viral hepatitis) is to coordinate research, schedule appropriate events and meetings and fund projects on HIV and viral hepatitis.
The Agency was created in 1988 to coordinate research on HIV/AIDS and as of 1 January 1999, the ANRS’ mission was expanded to include the task of coordinating and funding hepatitis C basic science and public health research. This role was expanded at the beginning of 2005 to all research on hepatitis B and C. Within a relatively limited time-frame, the ANRS was able to transfer its acquired HIV experience and adapt its reactivity and flexibility to the issues presented by hepatitis B and C clinical and public health research. As such, since 1999, the ANRS has funded 32 therapeutic trials, 31 physiopathological clinical research projects, four cohorts and over 300 basic research projects in the field of viral hepatitis. To reinforce research in the Middle East and Africa in 2007, the Agency created the ANRS site in Egypt, dedicated to clinical and basic research on hepatitis C genotype 4 (HCV-4).
The ANRS-funded projects led by university or clinical researchers result in, on average, 500 peer-reviewed publications per year on both HIV and viral hepatitis research, half of which are published in journals with an impact factor >5. At an international level, a survey carried out by Inserm shows that France is ranked second for hepatitis research (9.3% of total publications).
In 2011, the ANRS dedicated approximately 22% of its global budget to research in the domain of viral hepatitis.
The ANRS funds research projects in all disciplines including basic research projects, pre-clinical, clinical studies and projects in social sciences. Moreover, the ANRS is currently funding a vaccine research programme for Hepatitis C, carried out at the Vaccine Research Institute (VRI) in partnership with Université Paris Est Créteil.
In basic research, several aspects of hepatitis entry, assembly, replication and interaction with host cells are ANRS research priorities. In particular, the ANRS funds research in the following areas:
- Viral entry and assembly.
- Molecular mechanisms involved in host–virus interactions.
- Innate and adaptive immune responses to hepatitis infections.
- Mechanisms of viral persistence.
- Hepatitis C-induced carcinogenesis.
- Animal models.
The ANRS also supports a consortium of research groups devoted to the development and standardization of animal models, including humanized mouse models for studying viral hepatitis.
In addition, in collaboration with Inserm and the Universities of Paris VI and XI, the ANRS has set up a genomic platform on the site of the Pitié-Salpetrière Hospital. The platform is set up for ultra-deep sequencing for genotype/phenotype association studies. The platform provides support for both hepatitis and HIV research.
Clinical research in viral hepatitis
Despite notable progress in clinical research in the field of B and C viral hepatitis in recent years, a number of questions regarding patient care and the evolution of the disease remain unanswered. The ANRS therefore remains thoroughly involved in therapeutic trials, cohorts and physiopathology studies in the domain of viral hepatitis.
The ANRS supervises a unique clinical network in the field of viral hepatitis research in France, comprising 28 clinical units. Moreover, the agency funds 23 staff positions for Clinical Research Associates. The current patient register for HBV-/HCV-infected individuals is over 69 000; 700 patients are included in clinical trials and 2700 in cohorts, not including HIV/hepatitis co-infected patients.
The ANRS has strong ties with patient associations and community-based organisations, namely CHV (Collectif Hépatites Virales), which regroups several hepatitis organisations, including in particular SOS Hépatites. The associations provide advice on study protocols, in particular on trial information and patient consent sheets.
In general terms, patient care needs to be improved, and patients with treatment-failure need to be able to access novel combinations of molecules. Inversely, patients with successful therapies could benefit from simplified or shorter drug regimens.
Among our current priorities in clinical research on viral hepatitis are:
- Improve quality and effectiveness of medical care.
- Strategic evaluation of new HCV molecules (cohorts, co-infection studies).
- Understanding mechanisms of clearance.
Treatment options for chronically infected persons are at a paradigm shift. The two first-generation protease inhibitors, boceprevir and telaprevir, have been released in 2011 and are now to be used in the real-world. More than 70 new products directed against hepatitis B virus (HBV) and hepatitis C virus (HCV) are under clinical development. The ANRS has played a strong role in this therapeutic development by providing innovative support to the hepatitis community.
Viral Hepatitis mono-infection
- ANRS HC 29 BOCEPRETRANSPLANT. Pilot study on the Efficacy of PEG-IFN Alpha-2b – RBV – Boceprevir Triple therapy in Patients Infected with Genotype 1 HCV with Cirrhosis and Awaiting Liver Transplantation.
- ANRS CO 20 CUPIC. Compassionate Use of telaprevir and boceprevir in hepatitis C virus cirrhosis. National multicenter observatory in the setting of the French Temporary Authorization for Use (ATU) cohort to prospectively collect data and biological specimens. A total of 674 patients were included.
- ANRS CO 22 HEPATHER. In 2012, the ANRS set up this unique hepatitis cohort to identify biomarkers associated with the natural history of the hepatitis B and C viral infections. The cohort will give provide an extensive database on hepatitis B and C to improve therapeutic health strategies and accelerate research. The cohort will include 25 000 patients (10 000 HBV and 15 000 HCV). The cohort initially started in July 2012 in two pilot clinical sites, and will soon be extended to 25–30 sites in France. The cohort is a joint initiative between ANRS and AFEF (the French Association for the study of the Liver) and the partnership now also includes ANSM (the French national agency for drug and health products), the InVS, HAS (Haute Autorité de Santé), DGS (Direction Générale de Santé) and EFS. Pharmaceutical companies have also joined the collaboration. Thus, Hepather represents an innovative public–private partnership.
- ANRS HC 26 TelapreVIH. Pilot study of PEG-IFN/RBV-Telaprevir efficacy and tolerability in HIV-HCV co-infected patients who previously failed a PEG/IFN-RBV regimen.
- ANRS HC 27 BocepreVIH. A pilot study to assess the efficacy and safety of boceprevir in combination with PEG-IFN alfa/RBV, in subjects with HCV/HIV co-infection, in failure to a previous therapy of PEG-IFN/RBV. Both ANRS HC26 and HC27 trials are completed and results will be presented at CROI 2013 in Atlanta.
- ANRS HC 30 QUADRIH. Pilot study to assess the efficacy and safety of a Quadruple therapy with asunaprevir, daclatasvir, RBV and PEG-IFN alpha2a, in HIV and HCV genotype 1 or 4 co-infected patients, previously null responders to a standard PEG-IFN/RBV regimen (estimated to start Q1 2013).
The author has no disclosure.