Hepatitis Transformative Science Group

Strategic Plan and Research Agenda Hepatitis Transformative Science Group - 2011

Download Scientific Research Agenda (DOC - 52 KB)

Vision

  1. Provide effective therapy to all people with HIV coinfected with viral hepatitis
  2. Provide a platform for conduct of novel DAA trials in participants with HCV    

Drug selection

TSG will require direct, ongoing interactions with companies with promising DAA compounds to determine the best combinations of drugs to select in HIV/HCV coinfected individuals. Thus, partnership with companies studying 2-3 DAAs with or without interferon and ribavirin will be sought. We will revisit the long term plan every 6 months after evaluation of current studies reported in HCV mono and coinfected literature and at meetings in US and Europe.  Phase II studies will be planned in which evidence for or against efficacy will be obtained rapidly with relatively circumscribed enrollments. Studies in HCV mono- and co-infected participants that offer novel combinations of DAAs will have high priority, particularly in difficult to treat participants such as null responders to PEGIFN and ribavirin. Studies will incorporate genetic biomarkers (e.g. IL28B and ITPA genotyping) and viral kinetics (response guided therapy). We will work with drug companies to incorporate and validate the best predictive and prognostic candidate biomarkers for each drug regimen to determine their relevance in coinfection.

Enrollment

The Hepatitis TSG should be representative of the face of HIV in US and internationally. HTSG will encourage enrollment of underrepresented individuals in studies including women and persons of color.  This can be accomplished by direct interaction with other HIV groups, such as WIHS.  Timeliness is critical and the TSG will expect a timeline of concept sheet to study opening study of 6 months, with another 6 months to complete enrollment. This will mandate a rapid response from TSG, SDAC, Ops and teams.

TSG composition

Experts in viral hepatitis from ID and Hepatology who are representative of the ACTG as a whole; have experience in testing new HCV drugs; have contacts in industry; are able to focus on moving the hepatitis agenda forward; and show the ability to provide important and innovative input.

Training

The training of the next generation of investigators will be fostered by encouraging junior or mid level investigators to chair study teams with assistance from experienced ACTG investigators.

Current Challenges

Because of the complexity (in particular drug-drug interactions) of HCV DAAs, we will require close integration of laboratory and clinical scientists on teams. In particular, close interaction will be essential with virology (for response guided therapy and stopping rules to minimize unnecessary drug exposure; HCV resistance testing); pharmacology (drug-drug interactions); and genetics (IL28B, ITPA) groups in the ACTG.  For the TSG-industry partnership to be effective, timeliness will be essential.  This will place a premium on rapid protocol development and enrollment of study participants. To enable this, education of ACTUs about candidate selection, response guided therapy, drug-drug interactions and end stage liver disease will be critical to ensure successful execution of DAA studies.