Reuters Health Information: Sofosbuvir-ledipasvir effective for relapsed HCV-1
Sofosbuvir-ledipasvir effective for relapsed HCV-1
Last Updated: 2014-11-03
By Will Boggs MD
NEW YORK (Reuters Health) - The combination of sofosbuvir
and ledipasvir is effective for treating chronic hepatitis C
virus (HCV) genotype 1 infection that relapses after sofosbuvir
plus ribavirin therapy, according to results from a phase 2
"We were surprised because we had several patients with
cirrhosis and one with S282T mutation, which confers complete
resistance to sofosbuvir in vitro," Dr. Anita Kohli from
National Institutes of Health, Bethesda, Maryland told Reuters
Health by email. "All of these patients, who had risk factors
for relapse, achieved sustained virologic response 12 weeks
after completion of treatment (SVR12)."
In an earlier study, 17 of 54 patients treated with
sofosbuvir plus ribavirin for 24 weeks had relapse after
Dr. Kohli and colleagues investigated the safety and
efficacy of 12 weeks of treatment with sofosbuvir plus
ledipasvir in 14 patients with HCV genotype 1 infection who
relapsed after receiving sofosbuvir plus ribavirin.
Thirteen of these 14 patients had wild-type virus at the
time of relapse after sofosbuvir plus ribavirin treatment,
according to the November 4th Annals of Internal Medicine
All 14 patients treated with sofosbuvir plus ledipasvir had
HCV RNA levels below the lower limit of quantification by four
weeks, and this response was maintained through the end of
treatment and through 12 weeks after the completion of
In contrast to the decreases in hemoglobin levels seen
during sofosbuvir plus ribavirin treatment, there were no
significant changes in hemoglobin levels during the treatment
with sofosbuvir plus ledipasvir.
Renal function did not change significantly during
treatment, and there were no serious adverse events or
Common adverse events included myalgia and hypophosphatemia,
and most adverse events were mild.
"The low incidence of adverse events, low pill burden,
shorter treatment duration, and high efficacy demonstrated in
this group and other populations make this drug combination
attractive in a real-world setting," the researchers say.
"This could be the standard of care for patients who have
failed sofosbuvir and ribavirin," Dr. Kohli said. "The duration
between initial treatment failure after sofosbuvir and ribavirin
and retreatment with sofosbuvir and ledipasvir was over one
year. We do not know if patients would have responded in a
similar fashion had they been retreated sooner."
She added, "Resistance to HCV drugs is an evolving story and
seems quite different than with HIV. It will continue to evolve
with the introduction of new drugs and drug classes."
"The small sample size and only 1 patient with NS5B S282T
mutation after sofosbuvir plus ribavirin therapy may also
partially contribute to the high SVR rate of the study, because
the SVR rate may become lower when large sample size of patients
and large number of patients with NS5B S282T mutation were
included," Dr. Zhengwen Liu from First Affiliated Hospital,
School of Medicine, Xi'an Jiaotong University, Shaanxi, China
told Reuters Health by email.
"When the results, both the efficacy and the safety, will be
supported by future trials with large sample size of patients,
this treatment of sofosbuvir and ledipasvir would become one of
the standard of care for patients with HCV genotype 1 who
relapse with other treatment," concluded Dr. Liu, who has
studied the use of sofosbuvir-based treatment for chronic HCV
Dr. Eric M. Yoshida from University of British Columbia and
Vancouver General Hospital in British Columbia, Canada has also
published research on the treatment of chronic HCV infection. He
told Reuters Health by email, "This preliminary study provides
evidence that these patients can be re-treated successfully. It
is also noteworthy that these patients were drawn from a
previous study that had features of a 'difficult to treat'
population where the SVR rates were markedly worse than in
Gilead's phase 3 clinical trials. Therefore, this was truly a
'real world' patient population, which makes the outcome of this
paper all the more encouraging."
"Even though this study had only 14 patients, the
outstanding and dramatic response rates, with no significant
adverse effects, suggest that patients who relapse to sofosbuvir
DAA (direct antiviral agent) monotherapy and who cannot wait for
'better studies' or alternative drugs, should be treated until
there is clinical evidence to the contrary," Dr. Yoshida said.
"The population I am thinking about are those with established
cirrhosis who would otherwise be looking at future liver
transplant (and we know how difficult it is to get a transplant
given the disparity between available donor organs and the need
for liver transplantation)."
"When one has a patient in a desperate situation," he said,
"and there is a non-toxic, potentially effective therapy
available, it is not appropriate to be academically dogmatic
about how robust the published literature is or is not."
Ann Intern Med 2014;161:634-638.