Adding telaprevir (Incivo or Incivek) to pegylated interferon and ribavirin shortens the
duration of treatment and increases the likelihood of a cure for HIV-positive
men with acute sexually transmitted hepatitis C virus (HCV), according to study
findings presented last week at the 20th Conference
on Retroviruses and Opportunistic Infections (CROI 2013) in
Since the early 2000s, researchers have reported
outbreaks of apparently sexually transmitted HCV among HIV-positive gay and
bisexual men, first in the UK and continental Europe and later in Australia
and the US.
Acute hepatitis C often has no symptoms – or general symptoms like fever that can be mistaken
for flu – so most people do not seek treatment when they become
infected. HIV-positive people are in a unique position because those on
antiretroviral therapy (ART) are advised to receive regular liver function
tests to monitor for drug toxicity. Unexplained elevation of alanine aminotransferase (ALT) and other liver
enzymes should trigger viral hepatitis testing, which may reveal recent
It is well known that treating hepatitis C during
acute or recent infection, rather than waiting until the chronic phase (six
months after infection), is associated with high sustained response rates. In
one key study of hepatitis C monoinfected patients, 98% were cured with an
older formulation of interferon without ribavirin in just 24 weeks. But decisions
about whether to treat acute hepatitis C are not straightforward as treatment
comes with costs and side-effects and 15 to 25% of infected individuals will
spontaneously clear the virus without therapy.
Prompt treatment of acute hepatitis C improves
response rates for both HCV monoinfected and HIV/HCV co-infected people, but
co-infected people do not respond as well as those with HCV alone. Furthermore,
most studies show HIV-positive people are less likely to naturally clear HCV.
Daniel Fierer from Mt Sinai Medical Center in New York
City performed an open-label pilot study to see if adding the direct-acting HCV protease inhibitor telaprevir to interferon-based
therapy could increase response to treatment for acute HCV infection and
shorten the duration of therapy.
Since the mid-2000s, Fierer's team has
been following HIV-positive gay and bisexual men with sexually transmitted
hepatitis C, some of whom have shown unexpectedly rapid liver disease
progression in a relatively short period of time.
This analysis included 40 consecutively
enrolled eligible patients between July 2011 and September 2012. They were
sexually active HIV-positive men who have sex with men, who were recently found
to have newly elevated ALT and tested positive for HCV genetic material or
antibodies. Fierer explained that he receives referrals of such patients from
clinicians throughout the city.
If necessary, before starting
hepatitis C treatment, participants modified their antiretroviral regimen to
replace agents that have potential for drug-drug interactions with telaprevir. Acceptable
substitute regimens included ritonavir-boosted atazanavir (Reyataz), raltegravir (Isentress),
rilpivirine (Edurant) or efavirenz (Sustiva or Stocrin) with tenofovir/emtricitabine (the drugs in Truvada).
Within six months of their first
noted ALT elevation, participants were started on a 12-week triple combination
regimen of 750mg (or 1125mg if using efavirenz) thrice-daily oral telaprevir,
180mcg once-weekly injected pegylated interferon alfa-2a (Pegasys) and twice-daily weight-based oral ribavirin.
Of the 40 participants initially
enrolled, half were never treated. Seven people had HCV genotypes other than 1
(the only one for which telaprevir is indicated), five did not have insurance
that would cover telaprevir for this unapproved purpose and one had unmanageable
interactions with his ART regimen. In addition, five people spontaneously
cleared HCV before starting therapy and two refused treatment.
Most (85%) of the 20 treated participants
were white and the median age was 44 years. Eighteen had the more
difficult-to-treat HCV sub-type 1a. An unusually high proportion – 65% – had the favourable IL28B CC gene
pattern associated with good interferon response.
Fierer reported findings from an
interim analysis of sustained virological response rates at 4 weeks
post-treatment (SVR4). This is too soon to determine whether people are
actually cured, though a majority of post-treatment relapses among patients taking
direct-acting antiviral agentss appear to occur within this period.
Participants will be followed to determine how many have still have
undetectable HCV RNA at 12 weeks post-treatment (SVR12), which regulatory
authorities consider a valid measure of treatment success.
Seventeen out of 20 patients, or 85%,
had undetectable HCV RNA at the end of treatment and SVR4 at 4 weeks
post-treatment. Amongst participants with longer follow-up, 82% (14 out of 17)
achieved SVR12 and 79% (11 out of 14) reached SVR24. No relapses occurred among
people with end-of-treatment response.
Four participants were treated for
less than the full 12 weeks (ranging from 4 to 8 weeks) but all maintained HCV
suppression (at weeks 4, 12 and 24) after stopping therapy. Three people were
given a 'tail' of pegylated interferon/ribavirin alone after
finishing 12 week of triple therapy due to slow response or personal
Three people, all with unfavourable
IL28B CT or TT gene patterns, experienced treatment failure. Two were 'null responders' who did not suppress viral load below 1000 IU/ml
by week 4 (one with HCV sub-type 1a, one with 1b). In addition, one person with
sub-type 1a experienced late viral breakthrough at week 12 of treatment.
Among the nine participants who
modified their ART regimen before starting telaprevir, all maintained
undetectable HIV viral load.
Treatment was generally well
tolerated. Almost all participants reported itchiness (pruritis), though just
two developed skin rashes. One person stopped treatment at week 4 due to
anaemia that required a blood transfusion, and three others reduced their
ribavirin doses for this reason. One other participant stopped at week 5 due to
Summarising his results, Fierer said
that adding starting pegylated interferon/ribavirin treatment during acute
rather than chronic HCV infection doubles the sustained response rate in half
the time, and adding telaprevir is "twice as good" and cuts treatment
time in half again.
Fierer suggested that triple therapy
"should be [the] new standard for treatment of acute genotype 1 HCV in
HIV-infected patients". We should not wait for interferon-free therapy, he
added, because "treatment is prevention" and achieving a cure will
prevent HCV transmission to others.
Some experts expressed scepticism, however. Vincent Soriano from Hospital Carlos III
in Madrid said he might agree with "adding something
extra" for people with HIV, but was concerned about unnecessarily treating
people who might spontaneously clear HCV. Fierer noted that he did wait a few
months before starting therapy to allow this to occur. Fierer noted that he did wait a few months
before starting therapy to allow this to occur, and most people who were
excluded from treatment for one reason or other did not clear the virus.