Nearly all people with HIV and genotype 1-4 HCV co-infection
treated for 12 weeks with an interferon-free regimen of sofosbuvir (Sovaldi) plus daclatasvir (Daklinza) achieved sustained virological
response in the ALLY-2 trial, but 8 weeks did not work as well, according to a recent
report in the New England Journal of Medicine. Sub-studies presented this month at
IDWeek 2015 showed that this regimen is highly effective regardless of race or
specific antiretroviral regimen.
The advent of
direct-acting antiviral agents (DAAs) that can be used in all-oral regimens has
revolutionised hepatitis C treatment, offering options that are shorter, better
tolerated and more effective than interferon-based therapy. This is particularly
beneficial for HIV-positive people co-infected with hepatitis C virus (HCV),
who tend to have more rapid liver disease progression and do not respond as
well to interferon.
David Wyles of the University of California at San
Diego and fellow investigators with the ALLY-2 trial evaluated a combination of
Gilead Sciences' HCV NS5B polymerase inhibitor sofosbuvir and Bristol-Myers
Squibb's NS5A inhibitor daclatasvir without interferon or ribavirin. Results
were previously presented in part at this year's Conference on Retroviruses and Opportunistic
Infections (CROI).
Glossary
- IL28B
An inherited gene which all individuals have. There are three genotypes of IL28B; these influence response to hepatitis C and its treatment. People with CC genotype are more likely to spontaneously clear acute infection or (during chronic infection) respond well to interferon-based treatment. The other two genotypes are known as CT and TT.
This open-label study included 151 HIV/HCV
co-infected participants who had not received prior hepatitis C treatment and
52 treatment-experienced patients. Nearly 90%
were men, about 60% were white, about 35% were black and the median age was
approximately 55 years; 14% had compensated liver cirrhosis. More than
80% had HCV genotype 1 (68% with harder-to-treat subtype 1a), while about 15%
had genotypes 2 or 3 and a small number had genotype 4.
Almost all participants
were on antiretroviral therapy (ART), mostly with undetectable HIV viral load,
and the median CD4 count was above 500 cells/mm3. Those on ART
were permitted to use a wide variety of antiretrovirals. About half were taking HIV protease inhibitors
with most of the rest on NNRTIs or integrase inhibitors.
Previously untreated participants were
randomly assigned to receive 400mg sofosbuvir plus 60 mg daclatasvir once-daily
for either 8 or 12 weeks, while treatment-experienced patients were all treated
for 12 weeks. Daclatasvir doses were adjusted when administered with specific
antiretroviral medications based on prior drug interaction studies (down to 30mg when used with ritonavir-boosted HIV protease
inhibitors or up to 90mg when used with most NNRTIs).
The primary study endpoint was sustained
virological response at 12 weeks after the end of treatment (SVR12).
Overall SVR12 rates were 97% for
previously untreated people treated for 12 weeks, 76% for those treated for 8
weeks and 98% for treatment-experienced people treated for 12 weeks. Most
relapses occurred in the 8-week treatment arm.
Looking at genotype 1 alone, cure rates
were about the same: 96.4%, 75.6% and 97.7%, respectively. Everyone with
genotypes 2, 3 or 4 achieved sustained response. People with cirrhosis had
somewhat lower SVR12 rates in all treatment arms.
Sofosbuvir
plus daclatasvir was generally safe and well-tolerated. Serious adverse events
were uncommon (< 3% across treatment arms) and there were no adverse events
leading to treatment discontinuation. The most common side-effects were
fatigue, nausea and headache. Participants maintained HIV viral suppression and
stable CD4 counts.
These findings
show that sofosbuvir plus daclatasvir taken for 12 weeks is safe and effective
for HIV/HCV co-infected people, the study authors concluded. These results
support current hepatitis C treatment guidelines recommending that HIV-positive
and HIV-negative people should be treated the same for hepatitis C after taking
into account interactions with antiretrovirals.
As described in another study presented at CROI, Gilead's combination of
sofosbuvir and its NS5A inhibitor ledipasvir (the drugs in Harvoni) was also highly effective for HIV/HCV co-infected people
with genotype 1 in the ION-4 trial. Daclatasvir, however, is active against
other HCV genotypes that are more common outside the U.S. (known as 'pangenotypic').