Reuters Health Information: Oral drug combo effective for hepatitis C with HIV coinfection
Oral drug combo effective for hepatitis C with HIV coinfection
Last Updated: 2014-07-21
By Will Boggs MD
NEW YORK (Reuters Health) - The combination of two oral
drugs, sofosbuvir and ribavirin, was effective for hepatitis C
(HCV) infection in patients coinfected with HIV, in the
open-label, nonrandomized PHOTON-1 study.
Most regimens for HCV in patients with HIV coinfection have
included interferon and ribavirin along with a protease
inhibitor, but these combinations are poorly tolerated, and drug
interactions are problematic.
Dr. Mark S. Sulkowski from Johns Hopkins University School
of Medicine, Baltimore, Maryland and colleagues analyzed
sustained virologic responses (SVR) and adverse events in 223
patients with HIV and HCV genotype 1, 2, or 3 who received
sofosbuvir and ribavirin.
Treatment-naïve patients with HCV genotype 2 or 3 received
treatment for 12 weeks, and treatment-naïve patients with HCV
genotype 1 or treatment-experienced patients with HCV genotype 2
or 3 received treatment for 24 weeks.
As reported online in the July 23/30 issue of JAMA, after
two weeks of treatment, HCV RNA levels were no longer detectable
in 75% of patients with HCV genotype 1, 91% of treatment-naïve
patients with HCV genotype 2 or 3, and 98% of
treatment-experienced patients with HCV genotype 2 or 3.
By week 4, these proportions increased to 99% in genotype 1,
99% in genotype 2 or 3, and 100% in treatment-experienced
genotype 2 or 3 groups.
Three-quarters of treatment-naïve patients with HCV genotype
1 achieved SVR within 12 weeks of treatment, as did 88% of
treatment-naïve patients with HCV genotype 2, 67% of
treatment-naïve patients with HCV genotype 3, 92% of
treatment-experienced patients with HCV genotype 2, and 94% of
treatment-experienced patients with HCV genotype 3.
No one developed S282T or V321A mutations, and only four
patients showed emergence of L159F mutation. None of these
mutations conferred sofosbuvir resistance in vitro.
Only seven patients (3%) discontinued treatment due to an
adverse event. Most adverse events were mild to moderate in
severity, with fatigue, insomnia, nausea, and headache being
most commonly reported.
HIV RNA levels did not change significantly in patients not
receiving antiretroviral therapy at baseline, and only two
patients with suppressed HIV viremia on entering the study
experienced HIV viral breakthrough (one had documented
nonadherence to the regimen).
"Further studies of this regimen in more diverse populations
of coinfected patients are needed," the researchers add.
Dr. Michael S. Saag from the University of Alabama School of
Medicine in Birmingham wrote an editorial related to this
report. He told Reuters Health by email, "The standard of care
is rapidly changing. Right now, the ideal should be an all oral
regimen of either sofosbuvir plus ribavirin (as per the PHOTON
Study) or sofosbuvir plus simeprevir. However, sometime this
fall the FDA likely will approve several other oral agents:
ledipisvir, daclatisvir, and three new agents from AbbVie. When
this happens, it is likely that some combinations of those
drugs, with or without sofosbuvir or ribavirin, will emerge as
"As I point out in the editorial, we can't afford to pay for
these new drugs at current pricing," Dr. Saag said. "My hope is
that these newer agents will be priced substantially less than
sofosbuvir and, assuming all of the regimens having
(approximately) equal efficacy, allow pricing to become a major
determinant of which regimen is used preferentially. My sense is
that combinations of the newer agents will indeed be of similar
efficacy to the currently approved direct acting agents. We will
see if 'free market' forces are at play in the pharmaceutical
marketplace or not."
Dr. Saag offered his view on the open-label study: "From a
scientific perspective, there is no need for a comparison owing
to the large amount of existing data on Peg-IFN/ribavirin
regimens and its associated toxicity. From a practical
perspective, patients would not sign up for such studies, and I
don't blame them. The US FDA 'got this' and quite appropriately
allowed a fast-track process for the development of these newer
agents without requiring a randomized study vs. Peg-interferon
Dr. Raymond T. Chung from Massachusetts General Hospital in
Boston, who recently reviewed the antiviral treatment of HCV,
told Reuters Health by email, "Because of the very large number
of patients who are ineligible for or unwilling to be treated
with interferon-based regimens, the availability of an
effective, well tolerated all-oral treatment will now make
treatment possible. The lack of drug-drug interactions of this
regimen with contemporary antiretroviral regimens will also make
management of HCV in HIV coinfected persons much more
straightforward than prior approved regimens."
Dr. Chung agreed with Dr. Saag about the coming new drugs,
and cost issues. "We can expect even more attractive all-oral
regimens in the very near future that will further enhance cure
rates and shorten duration for persons with HCV infection,
including those with HIV coinfection," Dr. Chung said. "We will,
however, need to solve the cost problem, which threatens to
limit access of these curative therapies."
Dr. Curtis Cooper from the University of Ottawa in Ontario
reviewed the management of HCV/HIV coinfection in a recent issue
of HIV Medicine. Now, he told Reuters Health in an email, "the
paradigm in which HCV is often an after-thought for treatment in
coinfection will need to be reexamined - it now makes sense to
first cure HCV, thereby maximizing the safety and efficacy of
Dr. Sulkowski did not respond to a request for comments.