An interferon- and ribavirin-free regimen of
sofosbuvir/ledipasvir (Harvoni) taken
for just 6 weeks was enough to cure hepatitis C in HIV-positive people with recent
hepatitis C virus (HCV) infection if their HCV viral load was low, but those
with high HCV levels may need longer treatment, according to study findings
presented at the Conference on Retroviruses and Opportunistic Infections (CROI
2016) this week in Boston. Presenter Jürgen Rockstroh of
the University of Bonn predicted that HCV viral load will become a key factor
when making decisions about treating acute hepatitis C.
Studies done in the
interferon era showed that treating people during the acute stage of HCV
infection led to much higher response rates and required a shorter duration
than interferon-based therapy started during chronic infection.
The advent of
direct-acting antivirals (DAAs) in interferon-free regimens has made chronic hepatitis
C treatment shorter, better tolerated and more effective, and many experts
expected the same would be true for acute HCV infection. But a combination of sofosbuvir plus ribavirin taken for 12 weeks produced a sustained response rate of only 59% in a small study of HIV-positive men with acute hepatitis C presented at the recent 2015 AASLD Liver
There are currently no
specific direct-acting antiviral regimens approved for the treatment of acute
HCV infection. Current
guidelines recommend using the same DAA options as for chronic infection, or even continuing
to use interferon and ribavirin.
Prof. Rockstroh and colleagues conducted a
study to evaluate the safety and efficacy of short-duration treatment using the
HCV NS5B polymerase
inhibitor sofosbuvir and the NS5A inhibitor ledipasvir for
HIV-positive people with genotype 1 or 4 acute hepatitis C.
The analysis included 26 participants with HIV at five sites in Germany
and the UK. All were men, most were white and the mean age was 41 years. They
had acute HCV infection, defined as a positive HCV RNA test following a
negative HCV antibody or RNA test within the past 6 months, or elevated ALT/AST
during the past 6 months with no other known cause. About two-thirds had HCV
genotype 1a and the rest genotype 4; the mean HCV viral load at baseline was
5.4 log10 IU/ml.
could either be on antiretroviral therapy (ART) with suppressed HIV viral load
or not on ART with no plans to start. People on ART were using a variety of
antiretrovirals that can be co-administered with sofosbuvir/ledipasvir. The
most common regimens were efavirenz (Sustiva),
raltegravir (Isentress), dolutegravir
(Tivicay) or boosted atazanavir (Reyataz) plus tenofovir/emtricitabine
(the drugs in Truvada).
participants in this open-label study received sofosbuvir/ledipasvir in a fixed-dose coformulation (900/400mg) for 6 weeks.
The usual recommended duration of sofosbuvir/ledipasvir
for chronic hepatitis C treatment is 12 weeks, though easier-to-treat patients
with no prior treatment experience, no cirrhosis and low viral load can be
treated for 8 weeks.
After 6 weeks of therapy and 12 weeks of
post-treatment follow-up, 20 of 26 participants (77%) achieved sustained
virological response (SVR12), or continued undetectable HCV RNA. Four people experienced
virological failure – three relapses and one reinfection with a different HCV
genotype – and two were lost to follow-up.
All three relapsers had high baseline HCV
viral load above 7.0 log10 IU/ml; two had genotype 1a and one had genotype 4. No new NS5A or NS5B
resistance-associated viral variants were detected at the time of relapse.
Treatment was generally safe and well-tolerated
with one unrelated serious adverse event and no treatment discontinuations for
this reason. The most common adverse events were fatigue (7%), nasopharyngitis
(7%) and headache (6%), mostly mild or moderate. Safety profiles
were similar for people receiving boosted or unboosted tenofovir-based ART
Given that there were no relapses among
participants with baseline HCV RNA <6.9 log10
IU/ml, the researchers concluded, “acutely HCV-infected patients with a higher
viral load should be considered for longer duration of therapy.”
Rockstroh noted that although shorter interferon-based treatment works well for
people with acute infection, “unfortunately DAAs don't behave the same way.”
acknowledged that it is still not clear when is the best time to treat people
with acute HCV infection. About 25% of all people and 15% of people with HIV
and HCV co-infection with acute HCV infection will spontaneously clear the
virus. Many experts recommend waiting to see if treatment is really needed, but
the likelihood of transmitting HCV during this early period can be high.
considering guidelines for acute hepatitis C treatment, “everything is going to
be driven by viral load,” Prof. Rockstroh predicted.