Community-based Treatment of Chronic Hepatitis C Monoinfection and Coinfection With HIV in the District of Columbia
Condition: HCV HIV
MeSH terms: Hepatitis C; Hepatitis C, Chronic; Coinfection; Hepatitis
Study type: Interventional
Phase: Phase 4

Summary: 
      Background:

      - Treatment for Hepatitis C has changed a lot in the past 2 years. Most of this change comes
      from a combination of medicines that is yielding high cure rates. But its long-term effects
      are uncertain. One problem is that a lot of people need the treatment, but only a few
      specialists can give it. The success rate for Hepatitis C treatment by primary care doctors,
      nurse practitioners, or physician assistants is largely unknown. Researchers want to see how
      provider type affects treatment outcomes. They will conduct a large, community-based study in
      the District of Columbia.

      Objectives:

      - To see if people can be treated for Hepatitis C safely and successfully in community-based
      health centers.

      Eligibility:

      - Adults who need treatment for chronic Hepatitis C infection.

      Design:

        -  Participants will be screened with blood tests. Their current medicines will be
           reviewed.

        -  Participants will give researchers access to their medical records. Researchers will
           follow participants through these records.

        -  Participants will see a primary care or infectious disease provider. The provider will
           tell them about their treatment. They will be told how often they will visit the
           provider and how often they will have their blood drawn. They will get a calendar of
           study visits.

        -  Participants will take Harvoni for 8, 12, or 24 weeks. They will visit their care
           provider monthly.

        -  Participants will have monthly follow-up visits for up to 3 months after they finish
           their medicine.

        -  Participants will have yearly follow-up visits with their care provider for up to 10
           years.
    

Detailed description: 
      Treatment for hepatitis C has been revolutionized in the last 2 years with the advent of
      combination antiviral therapy yielding high cure rates; although, the long term effects of
      treatment remain uncertain. Use of these medications has been limited to clinical trial
      settings typically by highly specialized care teams in tertiary care hospitals. As the
      prevalence of hepatitis C is significant, there exists a significant imbalance between
      patients who require treatment and specialists who provide treatment. Success rates in
      treatment of hepatitis C by primary care doctors or physician extenders, such as nurse
      practitioners or physician assistants, is largely unknown.

      As such, we propose the first community-based, large scale, longitudinal study of directly
      acting antiviral (DAA)-based treatment for chronic hepatitis C, set in the District of
      Columbia. Within this study, approximately 600 HCV genotype 1 monoinfected and HCV/HIV
      coinfected subjects will be treated with ledipasvir/sofosbuvir (90 mg/400 mg) fixed dosed
      combination for 8-24 weeks, based on the medication labeling instructions, and followed for
      both immediate (SVR12) and long term (comorbid disease, cirrhosis, hepatocellular carcinoma,
      transplantation and mortality) outcomes over a 10 year study period. The study will be
      conducted exclusively in the District of Columbia clinics associated with the NIH DC
      Partnership for AIDS/HIV Progress (DC PFAP), which serves a population comprised primarily of
      minorities, with a high degree of negative predictors of treatment response. In this study,
      participants will be assigned to treatment either by (1) an ID or hepatology specialist, (2)
      primary care provider, or (3) physician extender. Please see Figure 1 study schema for an
      approximate distribution of subjects. Each of these provider groups will undergo uniform
      training on treatment of hepatitis C and management of adverse events prior to initiation of
      study. All subjects will sign informed consent and agree to treatment and follow up phases of
      the study. During the course of the study, subjcts will be clinically evaluated based on
      American Association for the Study of Liver Diseases (AASLD)/ the Infectious Diseases Society
      of America (IDSA) guidelines for the management of hepatitis C. Clinical data from subjects
      will be captured in a city wide cohort database, which will store guideline-driven data
      points from each clinic visit within the network.

      Through this trial we will explore the efficacy of managing hepatitis C subjects with
      directly acting antiviral therapy in an urban, community-based setting, and investigate the
      effect of provider type (specialist, primary care, or physician extender) on treatment
      outcome. We will detail the safety and tolerability of this treatment. We will assess
      variability in treatment outcomes between monoinfected and HIV-coinfected subjects. Finally,
      we will evaluate the public health impact of large-scale treatment of HCV infected subjects
      in preventing long-term clinical outcomes. As the first interferon (IFN)- and ribavirin
      (RBV)-free, urban community-based treatment utilizing new standard of care criteria, this
      study will serve as a model for implementation of similar practice patterns globally.
    

Intervention name(s): Ledipasvir 90 mg and Sofosbuvir 400 mg
Intervention type(s): Drug
Intervention description(s): Ledipasvir 90 mg and Sofosbuvir 400 mg fixed dose combination as per standard of care treatment guidelines
Other intervention name(s): Harvoni
Intervention MeSH terms: Sofosbuvir; Ledipasvir
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Community Based Research; Hepatitis C Virus and Human Immunodeficiency Virus; Ledipasvir/Sofosbuvir; Fixed Dose Combination; Sustained Viral Response