People who inject drugs (PWID) have higher rates of hepatitis C virus (HCV) than do other groups. Effective, safe new treatments called direct-acting antiviral agents (DAAs) have been developed recently. Unfortunately, PWID rarely get these treatments. The drugs are expensive, so insurers often do not cover the cost of DAAs. Sometimes doctors hesitate to prescribe DAAs because they are concerned that PWID won’t take their medication or that these patients might become reinfected.
Several good models for treating PWID exist. One of them is to provide directly observed treatment (DOT). Another model provides treatment to PWID with the support of patient navigators (PN), public health workers who offer support and education to patients. Though both the DOT and PN models have been successful, we still don’t know which model works best.
In this study, we will study both DOT and PN models for treating HCV in PWID. Our goal is to find out which model produces the best results and is preferred by patients. Up to 1,000 HCV-infected PWID will participate in the study in eight sites around the country. We will randomize patients into either the PN or the DOT groups. Patients who end up in the PN group will get a biweekly blister pack of medication to take home. Their PN will provide education and support. We will find out whether patients adhered to medication using an electronic adherence monitoring system. Patients who are randomly assigned to the DOT group will take their medication in front of a staff member.
In our analysis, we will examine which treatment works better. Specifically, we will compare the proportion of patients in each arm who:
- initiate treatment;
- adhere to medication (that is, take at least 80 percent of their medication);
- complete treatment;
- are cured so that they have no virus in their blood; and
- become reinfected.
Patients who are cured will be followed for two years to determine whether they become reinfected. In addition, we will examine the proportion of patients in each arm who develop resistance, which means that the virus in their blood may no longer respond to medication. This will be one of the first studies to conduct research to understand why some patients develop resistance while others do not.
Patients will be recruited from many different places: methadone clinics, community health centers, needle exchange programs, community-based organizations, homeless programs, and groups of PWID who are participating in other research studies. The eight sites are: New York City (Montefiore Medical Center), Baltimore (John Hopkins University), Providence (Warren Alpert Medical School of Brown University), Boston (Harvard Medical School), Cincinnati (University of Cincinnati), Seattle (University of Washington), San Francisco (University of California, San Francisco), and Albuquerque (University of New Mexico).
How patients receive their study medication will depend on where they are getting the treatment. Some patients will be enrolled from methadone clinics. If they are randomized to the DOT group in the study, then they’ll get their medication each day at the same time they get their methadone. Patients enrolled from clinics in the community and randomized to DOT will decide whether to take their medication at the clinic, at home, or within the community (for example, at a coffee shop or other gathering place). Patients randomized to PN will receive support from a PN and also from a peer-led support group.
A national stakeholder group led by the Centers for Disease Control and Prevention will help guide our project. Other stakeholders that have helped us create our study design or that have committed resources include Treatment Action Group, National AIDS Treatment Advocacy Group, Harm Reduction Coalition, National Alliance for Medication Assisted Recovery, Medication Assisted Recovery Services, Hepatitis Support and Mentor Group, Project Inform, Hepatitis Education Project, National Viral Hepatitis Roundtable, New York State Department of Health, New York City Department of Health, Gilead, OraSure Technologies, Quest Diagnostics, and Monogram Biosciences.
We have three aims for our study:
- Aim 1: Determine in a randomized trial whether either of two models (PN or DOT) provided on-site at methadone programs and community health centers is more effective for enhancing HCV treatment.
- Aim 2: Determine the factors associated with developing drug resistance and reinfection. We will pool all the patients from all the sites and both treatment arms together to explore what proportion of subjects develops resistance and reinfection. We will examine how patterns of adherence affect the development of resistance.
- Aim 3: Understand which patient-level factors affect treatment outcomes. First, we will measure important psychosocial factors, such as homelessness, co-morbid mental illness, lack of trust in providers, poor social support, high levels of shame and stigma, and poor knowledge and motivation. We will examine how these patient-level factors are associated with poor treatment outcomes. Second, we will use qualitative methods to learn from patients and from PNs about their perception of the program. Patients and PNs may have special insight into why some patients succeed in the program and others do not. We will interview both patients who succeeded in treatment (that is, they initiated the treatment, took the medication as directed, were cured, and stayed healthy) and patients who did not succeed in treatment (those who dropped out, did not take all their medications, were not cured, or got sick again). Comparing the experiences and perceptions of patients who did well with treatment to those who didn’t will help us understand better how to improve the intervention in future studies.