A combination of
sofosbuvir (Sovaldi) and ribavirin
cured more than 90% of hepatitis C in people living with HIV and acute
hepatitis C virus (HCV) infection in a small study, but a similar trial of the
same regimen saw a much higher relapse rate, according to a pair of
presentations at the 2015 AASLD Liver Meeting in November.
Research done in the era
of interferon-based therapy showed that treating people during the acute stage
of HCV infection led to higher response rates and required a shorter duration
than treatment started during chronic infection.
The advent of direct-acting
antivirals used in interferon-free regimens has made treatment for chronic HCV infection
shorter, better tolerated and more effective, and the same may be true for
acute infection. Researchers previously showed that the first-generation HCV protease
inhibitor telaprevir (Incivo) plus pegylated interferon and ribavirin
produced a high cure rate for acute hepatitis C, but this triple combination
was poorly tolerated.
Susanna Naggie of
Duke University Medical Center presented findings from the ACTG A5327 SWIFT-C
trial, which tested a combination of the HCV polymerase inhibitor sofosbuvir
plus ribavirin for 12 weeks in people with HIV and HCV co-infection diagnosed with
acute HCV. (Not to be confused with the C-SWIFT trial evaluating sofosbuvir plus
grazoprevir/elbasvir.)
This multicentre trial enrolled 17 participants
with acute HCV, defined as HCV antibody seroconversion or newly detectable HCV
RNA in the prior six months, or liver enzyme elevations with detectable HCV RNA
in people without a recent HCV test. Participants were enrolled within 12 to 24
weeks from the first evidence of HCV infection.
All 17 participants were men, 65% were Hispanic,
the median age was 45 years and 76% reported never having injected drugs (suggesting
the possibility of HCV sexual transmission). Most (88%) had HCV genotype 1,
with one person having genotype 2b and another undetermined. The median
baseline HCV RNA was 2,280,000 IU/ml. Participants were all on antiretroviral
therapy (ART) with undetectable HIV viral load and the median CD4 cell count
was approximately 500 cells/mm3.
All participants in this single-arm, open-label
trial received 400mg once-daily sofosbuvir plus 1000-1200 mg/day weight-based
ribavirin for 12 weeks.
The primary endpoint was sustained virological
response, or continued undetectable HCV viral load at 12 weeks after completion
of treatment (SVR12). Results were compared against the historical SVR12 rate
of 60% using pegylated interferon/ribavirin for 24-48 weeks.
All 17 participants completed the study with no
treatment discontinuations or dose adjustments, and all had undetectable HCV
RNA at the end of treatment. However, seven participants experienced HCV
relapse or reinfection, leaving 10, or 59%, with SVR12, which did not meet the
criteria for non-inferiority to pegylated interferon/ribavirin.
No serious adverse events occurred, but about
half of participants experienced grade 2 (moderate) or higher adverse events.
"A 12-week course of sofosbuvir and
ribavirin achieved suppression of HCV in all participating HIV-infected men
with acute HCV infection, but the relapse rate was high," the
investigators concluded. "The mechanism(s) for the high relapse observed
is unclear, but other treatment options are needed for this population."
In the second study,
Daniel Fierer of Mount Sinai School of Medicine and colleagues tested
sofosbuvir plus ribavirin in people with HIV and acute hepatitis C who were
ineligible for or unable to enrol in SWIFT-C.
This single-centre
study enrolled 13 men with recent HCV infection – 11 with primary (first-time)
infection and two with reinfection after previous HCV clearance. Reinfection was defined as detectable HCV after being undetectable for
the prior 12 weeks.
About half of participants were white, two were
black, two were Hispanic and one was Asian; the median age was 43 years. All
had HCV genotype 1 (10 with harder-to-treat subtype 1a and two with 1b). The median
HCV RNA level was approximately 32,000 copies IU/ml, but two men had a very
high viral load greater than 10,000,000. All but two were on ART with
undetectable or low HIV viral load and the median CD4 count was 545 cells/mm3.
Participants were observed for 12 weeks before
starting treatment to see if they spontaneously cleared HCV, and one man did
so. The rest began treatment at a median 22 weeks after acute HCV was detected.
Again, everyone was treated with 400mg once-daily sofosbuvir plus weight-based
ribavirin for 12 weeks.
In this study, all 12 treated participants
completed 12 weeks of therapy, and 11 (92%) achieved SVR 12. One person
experienced HCV relapse between weeks 4 and 9 post-treatment. This man, with
HCV reinfection, had a low peak ALT and baseline HCV RNA >1,000,000 IU/ml
before starting treatment and had previously experienced treatment failure with
interferon/ribavirin during primary infection.
The most common adverse events were irritability
and insomnia, but these did not limit treatment.
"Sofosbuvir + ribavirin for 12 weeks was highly
effective in the treatment of acute genotype 1 HCV in HIV-infected men in this
'real-world' setting using broad enrolment and treatment criteria," the
researchers concluded. "The reasons for the different outcome between this
study and ACTG A5327 are not known."
Given the availability of newer direct-acting
antivirals, they suggested that rather than confirming this regimen in larger
studies, it would be better to test other regimens without ribavirin. The ACTG A5327 trial is now evaluating sofosbuvir/ledipasvir (Harvoni) for acute hepatitis C.