Research carried out by Mount Sinai Medical Center, New
York, found that non-adherence was the strongest risk factor for
treatment failure in people taking sofosbuvir/ledipasvir (Harvoni). The main reasons cited for non-adherence were failing to
take medication as prescribed and hospitalisation.
The findings were presented at the 2016 AASLD Liver Meeting in
Boston earlier this month.
Although hepatitis C treatment failure rates are low, the
cost of re-treatment is a substantial barrier to cure in people with hepatitis
C who do experience the failure of a direct-acting antiviral regimen.
Non-adherence may result in drug resistance, potentially reducing the response
to subsequent therapy.
Once treatment is prescribed and payment for treatment
through insurance or Medicaid is approved, people may still face a number of
structural barriers to adherence, such as prohibitive co-payments required for
each refill of medication, homelessness, incarceration or shift work patterns.
Motivational and educational barriers to adherence, such as
lack of knowledge about pill-taking or the need for adherence, have been less
The study investigated the relationship between treatment
failure and non-adherence at a Mount Sinai Medical Center outpatient clinic in
people receiving sofosbuvir/ledipasvir for either 8 or 12 weeks.
Forty-three people experienced post-treatment viral relapse.
A sample of 101 patients treated at the same clinic who achieved SVR24 was
compared with the treatment failure group to identify risk factors for
The 43 people who experienced treatment failure had an
average age of 59 years, 53.5% were African American, 25.6% Hispanic and 20%
white. Eighteen of the 43 people had prior experience of hepatitis C
treatment (four with direct-acting antivirals) and 21 had cirrhosis (17 Child-Pugh A, 4 Child-Pugh B). The predominant genotypes were 1a (26) and 1b (12). None
had genotype 3 infection.
Five people received an 8-week course of treatment, 33
received a 12-week course of treatment and five received a 24-week course of
treatment. Thirty-eight of 43 people achieved undetectable HCV RNA on
treatment and none experienced subsequent viral breakthrough on treatment.
Viral relapse had occurred in 37 of 38 patients by the time
of the first post-treatment visit (variable periods elapsed before the first
post-treatment visit) and, in the remaining patient, by the time of the 24-week
Thirty-three of 43 people reported to their physician that
they had been adherent. Non-adherence was defined as missing at least seven
doses of sofosbuvir/ledipasvir. Reasons for non-adherence were not taking
medication as prescribed (5 patients), hospitalisation (3), loss of medication
(1), failure to refill medication (1) and side-effects (1).
Multivariate analysis found significant associations between
treatment failure and the following factors:
- Black race: odds ratio (OR) 3.84 (95% CI
1.67-8.86) (p = 0.001)
- Male sex: OR 3.86 (95% CI 1.37-10.85) (p = 0.007)
- Non-adherence: OR 16.3 (95% CI 3.26-81.92) (p < 0.0001)
The only significant difference between those who adhered
and those who were non-adherent was a modest difference in the number of clinic
visits during the treatment period; non-adherent people visited the clinic an
average of 3.9 times, adherent people 2.6 times (P = 0.03).
The researchers concluded that their findings “underscore
the need for providers to clearly communicate dosing information and to ensure
that patients have access to an uninterrupted supply of medication.” They
suggested that pre-treatment adherence counselling and a pill bottle monitoring
system may also improve SVR rates.
The content of pre-treatment counselling needs to be
tailored to patient characteristics and pre-existing beliefs about treatment,
as well as addressing lifestyle factors that might affect adherence.
Previous research has shown that adherence to
interferon-free hepatitis C treatment declines with time on treatment, with
patients frequently citing the perception that treatment was working as a
reason for missing doses. Lack of privacy was cited frequently as a reason for
missing doses in the same study (Petersen,
CROI 2014, poster #667). Greater pill burden was also associated with
non-adherence, a problem encountered in other disease areas along with greater
non-adherence with multiple daily doses. Psychiatric issues and substance use may
also affect treatment adherence.
Readiness Evaluation and Preparation for Hepatitis C Treatment (PREP-C) tool
has been designed to allow
healthcare providers to conduct a psychosocial evaluation of readiness to take
hepatitis C treatment, and to identify areas of psychosocial
functioning that can be improved before a patient begins HCV treatment to
ensure that treatment will be successful.
Patients can also assess their own readiness for treatment
by using the
HepCure app, developed by the Mount Sinai hepatitis C team. The app can
also be used to set adherence reminders and to communicate with healthcare
providers on treatment adherence, side-effects and lab test results.