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Daclatasvir plus sofosbuvir cures HCV for most people with HIV and HCV co-infection in French compassionate use programme
Liz Highleyman, 2015-08-03 07:50:00
Interferon-free treatment using daclatasvir (Daklinza) and sofosbuvir (Sovaldi),
with or without ribavirin, was well-tolerated and produced sustained
virological response rates of 95-100% for people with HIV and HCV co-infection and
advanced liver disease, according to a presentation at the Eighth International AIDS Society
Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) last week
in Vancouver, Canada.
These results, from a French programme
that provides new therapies to people in need of treatment prior to
regulatory approval, demonstrate
that outcomes in the 'real world' can be as good as those seen in clinical
trials of these drugs.
It is estimated that about one-third of people with HIV worldwide are
have hepatitis C virus (HCV) co-infection. Over years or decades, chronic
hepatitis C can progress to serious liver disease including cirrhosis and liver
cancer. People with HIV and HCV co-infection typically experience faster disease
progression than those with HCV alone, and liver disease is a leading cause of
illness and death among people living with HIV.
People with HIV do not respond as well as HIV-negative people to
interferon-based hepatitis C treatment and they may have worse side-effects, so
they especially stand to benefit from new direct-acting antiviral agents (DAAs)
that can be used in interferon-sparing regimens.
Dominique Salmon of Hôpital Cochin in Paris presented findings from an analysis of people with HIV and HCV co-infection receiving Bristol-Myers
Squibb's HCV NS5A inhibitor daclatasvir plus Gilead Sciences' NS5B polymerase
inhibitor sofosbuvir in a compassionate use programme at more than 200 centres
Compassionate use programmes provide experimental drugs prior to
approval for people with an urgent need for treatment who cannot use or do
not benefit from existing therapeutic options. This analysis looked at people
seeking hepatitis C treatment in a real-world clinical care setting, rather
than as part of a clinical trial. Sometimes outcomes among people treated in
the real world are not as good as trial results because trials may select participants
who are most likely to benefit and often provide intensive monitoring and
The researchers looked at 564 people with co-infection who accessed
daclatasvir and sofosbuvir through the compassionate use programme between
March and October 2014. (The two drugs received European Union marketing
approval in January 2014 and August 2014, respectively.) Within this group, the
primary efficacy analysis included 147 people who had HCV viral load measurements
available at 12 weeks post-treatment, allowing determination of sustained
virological response (SVR12).
Nearly three-quarters of the study participants were men and the
median age was 52 years. The most common HCV genotype was 1a (51%), followed by
4 (20%), 1b (16%) and 3 (10%). About 85% had previously been treated for
hepatitis C, usually with interferon.
To be eligible for compassionate use, participants had to
have either advanced liver fibrosis (Metavir stage F3 or higher) or less
extensive fibrosis with extra-hepatic manifestations. People awaiting liver
transplants or who had HCV recurrence after transplantation were also eligible.
A majority (76%) had liver cirrhosis, generally with well-compensated disease.
Most were categorised as Child-Pugh class A, meaning modest loss of liver
function and high short-term survival probability.
The participants were on antiretroviral therapy (ART) with
undetectable HIV viral load. More than 60% were taking ART regimens that
included an integrase inhibitor, while 36% used HIV protease inhibitors and 24%
used NNRTIs. The median CD4 cell count at baseline was 592 cells/mm3.
The recommended hepatitis C treatment regimen was 60mg
daclatasvir plus 400mg sofosbuvir, both taken once daily; however, the
daclatasvir dose was adjusted up or down depending on which antiretrovirals the participants were taking. While 68% were treated for the recommended duration of 24
weeks, 31% finished therapy at 12 weeks. Ribavirin could be added at the
discretion of the treating physician and was used by 10% of the participants.
The overall sustained virological response rate at 12 weeks post-treatment (SVR12)
was 97%. Cure rates were similar for people treated with daclatasvir plus
sofosbuvir alone for 12 or 24 weeks (98% vs 97%, respectively). All of the 14
people who added ribavirin were cured with either treatment duration. All participants with genotype 3 and all but one with genotype 4 were cured.
Non-responders included nine relapsers and two people with viral breakthrough
while on therapy.
The results, Salmon said, show that there was no extra benefit from adding
ribavirin or extending treatment duration from 12 to 24 weeks. Cirrhosis status
and HCV genotype also did not affect the likelihood of sustained response. This
is important because while there are other effective treatment options for
genotype 1 – namely Gilead's sofosbuvir/ledipasvir coformulation (Harvoni), Janssen's simeprevir (Olysio) and AbbVie's Viekirax/Exviera regimen – genotype 3 does not respond well to these other
These compassionate use response rates match the
96-98% SVR12 rates for most
people with HIV and HCV co-infection without cirrhosis treated for 12
weeks in the phase 3 ALLY-2 trial; in that study response fell to just 76% for
people treated for only 8 weeks. (ALLY-2 results are published in the July 21
online edition of the New England Journal
In a safety analysis that included 564 people taking treatment,
there were just two treatment-related serious adverse events and two people
discontinued treatment due to adverse events. HIV remained under control during
hepatitis C treatment.
Based on these findings, the researchers concluded
that daclatasvir plus sofosbuvir, "provided high
SVR12 rates in this real-world, interim analysis in HIV/HCV coinfected
patients," and that daclatasvir plus sofosbuvir with or
without ribavirin "was generally well tolerated
and compatible with a wide range of antiretrovirals."