Clinical Trial Summary
Injection drug users (IDUs) constitute 60% of the approximately 5 million people in the U.S.
infected with hepatitis C virus (HCV). HCV treatment leading to sustained viral response
(SVR) is associated with increased survival. However, IDUs have had poor access to HCV care
and their success in HCV treatment has been limited. With direct-acting antiviral agents, HCV
treatment delivered within large clinical trials leads to SVR or cure in over 70% of
genotype-1 infected patients, compared to 45% with previous therapies. However, SVR rates are
as low as 14% in real-world settings. The majority of patients who fail to achieve SVR will
develop drug resistance, but the optimal adherence level to minimize resistance is unknown.
If HCV treatment continues to be delivered within current models of care, most IDUs will not
only fail treatment and develop resistance, but may transmit resistant viruses to others. We
have previously developed a multidisciplinary model of HCV care which integrates on-site
primary care, substance abuse treatment, psychiatric care, and HCV-related care within opiate
agonist treatment clinics. To maximize treatment outcomes, we piloted two models of intensive
HCV-related care: directly observed therapy (DOT), and concurrent group therapy (CGT). In our
DOT model, pegylated interferon is administered once weekly, if applicable, and one daily
dose of oral medication is administered at the methadone window. In our CGT model, patients
initiate HCV treatment within a once weekly treatment group which provides powerful social
support to mitigate fears of side effects, promote efficient education, and deliver weekly
injections, if applicable. It is unknown whether either model is better or more
cost-effective than standard on-site care.
PREVAIL 1: In the proposed study, 150 IDUs with chronic HCV (genotype 1) will be recruited
from methadone clinics and randomized to one of three models of care: DOT; concurrent group
treatment; or standard on-site care. Our specific aims are: 1) To determine whether either of
two intensive on-site HCV treatment models (DOT or concurrent group treatment) is more
efficacious than standard on-site treatment for enhancing adherence and SVR, and decreasing
drug resistance; (2) To determine the incidence and factors associated with the development
of drug resistance in IDUs; (3) To perform cost and cost-effectiveness analyses of each
model; (4) To examine the impact of HIV coinfection on adherence and virologic outcomes among
HCV-infected IDUs.
PREVAIL 2: In the proposed study, 60 IDUs with chronic HCV (genotypes 1 2, 3 and 4) will be
recruited from opiate agonist treatment programs and started on HCV treatment. Subjects will
be offered the choice of model of care (either standard on-site, DOT, or concurrent group
treatment). Our specific aims are: (1) to determine rates of adherence and SVR in a cohort of
opiate agonist treatment patients initiating treatment with sofosbuvir-based regimens and (2)
to determine adherence rates over time in drug users (genotype 3 and genotype 1 /
IFN-ineligible) initiating a 24 week IFN-free regimen.
PREVAIL 3: In the proposed study, 60 IDUs with chronic HCV (genotype 1 and 4) will be
recruited from opiate agonist treatment programs and started on HCV treatment. Subjects will
be offered the choice of model of care (either standard on-site, DOT, or concurrent group
treatment). Our specific aims are: (1) to determine rates of adherence and SVR in a cohort of
opiate agonist treatment patients initiating treatment with oral DAA combination of
sofosbuvir and simeprevir or fixed dose of sofosbuvir and ledipasvir and (2) to determine
adherence rates over time in drug users.
PREVAIL 1: In the proposed study, 150 IDUs with chronic HCV (genotype 1) will be recruited
from methadone clinics and randomized to one of three models of care: DOT; concurrent group
treatment; or standard on-site care. Our specific aims are: 1) To determine whether either of
two intensive on-site HCV treatment models (DOT or concurrent group treatment) is more
efficacious than standard on-site treatment for enhancing adherence and SVR, and decreasing
drug resistance; (2) To determine the incidence and factors associated with the development
of drug resistance in IDUs; (3) To perform cost and cost-effectiveness analyses of each
model; (4) To examine the impact of HIV coinfection on adherence and virologic outcomes among
HCV-infected IDUs.
PREVAIL 2: In the proposed study, 60 IDUs with chronic HCV (genotypes 1 2, 3 and 4) will be
recruited from opiate agonist treatment programs and started on HCV treatment. Subjects will
be offered the choice of model of care (either standard on-site, DOT, or concurrent group
treatment). Our specific aims are: (1) to determine rates of adherence and SVR in a cohort of
opiate agonist treatment patients initiating treatment with sofosbuvir-based regimens and (2)
to determine adherence rates over time in drug users (genotype 3 and genotype 1 /
IFN-ineligible) initiating a 24 week IFN-free regimen.
PREVAIL 3: In the proposed study, 60 IDUs with chronic HCV (genotype 1 and 4) will be
recruited from opiate agonist treatment programs and started on HCV treatment. Subjects will
be offered the choice of model of care (either standard on-site, DOT, or concurrent group
treatment). Our specific aims are: (1) to determine rates of adherence and SVR in a cohort of
opiate agonist treatment patients initiating treatment with oral DAA combination of
sofosbuvir and simeprevir or fixed dose of sofosbuvir and ledipasvir and (2) to determine
adherence rates over time in drug users.
