Nearly three-quarters of HIV/HCV co-infected patients
in the French HEPAVIH cohort achieved end-of-treatment virological response to
hepatitis C treatment with telaprevir plus pegylated interferon/ribavirin, even
though one-third had potential contraindications to this type of therapy,
according to a report at the 7th International
AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) this
month in Kuala Lumpur.
People with HIV experience more rapid
liver disease progression, on average, than people with hepatitis C virus (HCV)
alone, and generally do not respond as well to interferon-based therapy. This
population has an urgent need for better treatment options, but adding the HCV
protease inhibitors boceprevir (Victrelis)
or telaprevir (Incivo or Incivek) can increase the risk of
side-effects and drug-drug interactions with antiretrovirals for HIV.
Dominique Salmon from Cochin Hospital in Paris
and fellow investigators with the ANRS CO13 HEPAVIH cohort study looked at treatment
access and outcomes among co-infected patients in a 'real-life' clinical
practice setting. In clinical trials triple therapy with boceprevir or
telaprevir improved response rates by approximately 30% over pegylated
interferon/ribavirin alone, she noted, but trials often have restrictive entry
criteria that exclude many people who need treatment in the real world.
The prospective HEPAVIH cohort included 1324 co-infected individuals
with genotype 1 HCV who were followed at 24 clinical centres in France between
January 2011 and June 2013. The researchers compared outcomes among 320
eligible patients – 114 (36%) who started triple therapy and
206 (64%) who did not – looking at contraindications, early treatment
response and adverse events.
Participants, with an
average age of about 48 years, had well controlled HIV: 85% had undetectable
HIV RNA and the median CD4 count was 555 cells/mm3. About 70% had
harder-to-treat HCV subtype 1a. Patients who were treated had
more severe fibrosis. Among people who started triple therapy, 30%
had liver cirrhosis and 71% were non-responders to prior hepatitis C treatment.
Among those who did not start therapy, 14% had cirrhosis and only 25% had been
Looking at potential contraindications,
the most common was psychiatric conditions, reported by 23% of those who
started triple therapy and 26% who did not. This is considered a barrier to
treatment because interferon can cause or worsen depression and other mental
The next most common reasons
for not starting treatment were current active drug use (reported by 9% of
non-starters), heavy alcohol consumption (5%) and use of non-compatible
antiretroviral drugs likely to interact with HCV medications. One active drug user
and two people on incompatible antiretrovirals started triple therapy anyway.
About 3% of both starters and non-starters had decompensated cirrhosis or liver
cancer. Anaemia and low platelet counts were uncommon in both groups.
Overall, 34% of people who
started triple therapy had at least one contraindication compared with 42% of
non-starters – not a significant difference.
Among those who started
triple therapy, 80 patients (70%) did so outside a clinical trial. Most used
telaprevir (71% overall, 84% outside trials), followed by boceprevir (21%
overall, 16% outside trials) and other investigational direct-acting antivirals
(nine patients, all in trials). All were on combination antiretroviral therapy,
with raltegravir (Isentress) and
atazanavir (Reyataz) being the most
commonly used drugs.
Salmon did not describe the
specific hepatitis C regimens, but telaprevir triple therapy is usually taken
for 12 weeks, followed by pegylated interferon/ribavirin alone for up to 36 more
weeks depending on early response, with a full 48-week course recommended for
people with HIV. Boceprevir triple therapy lasts for up to 48 weeks, again with
a long course recommended for hard-to-treat patients including those with HIV.
After 4 weeks on treatment
69% of telaprevir recipients experienced rapid virological response, 80% still
had undetectable HCV RNA at the end of the 12-week course of triple therapy and
74% remained undetectable at week 24. Boceprevir recipients responded more
slowly, with only 20% having undetectable HCV at week 4, rising to 60% at both
weeks 12 and 24. Salmon noted that these response rates were in on the same
order as those seen in phase 3 trials.
Response rates varied based
on known predictive factors. Among telaprevir recipients, 24-week virological
response rates were 82% for treatment-naive patients, 80% for previous
relapsers and 68% for prior non-responders. Those with HCV subtype 1b responded
better than those with 1a (90% vs 69%), as did people without cirrhosis
compared with cirrhotics (77% vs 67%). Patient numbers were too small to make
meaningful comparisons among boceprevir recipients.
Turning to tolerability, the
most common side-effect was anaemia (haemoglobin <9g/dL), seen in 35% of telaprevir
recipients and 20% of boceprevir recipients. Three people used erythropoietin
(EPO) and nine required blood transfusions. In the telaprevir group 16%
developed skin rash and 8% reported anal pruritis or itching, neither of which
was reported by boceprevir recipients.
Overall, one-quarter of
participants stopped treatment prematurely, most often due to non-response (67%
of telaprevir discontinuations and 80% of boceprevir discontinuations). Six
patients stopped due to various adverse events, including two cases of severe
anaemia in the telaprevir group.
"Triple therapy was
started despite potential contraindications to treatment, mainly psychiatric
disorders, present in 34% of treated patients," the researchers
summarised. "On the contrary, non-treated patients did not have
contraindications in 58% of the cases."
"The rate of
virological responses at week 24 was high (74% for telaprevir and 60% for
boceprevir), with a trend for a better virological response in genotype 1b and
non-cirrhotic patients," they concluded.
Salmon added that these
results must be viewed with caution until assessment of sustained virological
response (SVR), as relapse can occur during the last months of therapy or after
the end of treatment. (A cure is typically defined as continued undetectable
HCV at 12 or 24 weeks post-treatment, known as SVR12 or SVR24).