people treated with telaprevir (Incivo)
triple therapy are significantly more likely to achieve sustained virological
response, or a cure, than those treated with pegylated interferon/ribavirin
alone, according to final results from Study 110 presented yesterday at The Liver Meeting (the 63rd Annual Meeting of the American Association for
the Study of Liver Diseases, or AASLD) in Boston.
approval of the first direct-acting hepatitis C drugs ushered in a new treatment paradigm. The hepatitis
C virus (HCV) protease inhibitors telaprevir (produced by Janssen/Vertex) and
boceprevir (Victrelis, produced by
Merck) are licensed in Europe and the US for HCV monoinfected patients, but co-infected people also have a
pressing need for better hepatitis C treatment, especially since liver disease
tends to progress faster in this population.
Mark Sulkowski from Johns Hopkins
University School of Medicine presented final 24-week sustained virological
response (SVR24) results from a randomised, controlled phase II trial
evaluating triple therapy using telaprevir plus pegylated interferon and
ribavirin in previously untreated co-infected patients with difficult-to-treat
HCV genotype 1. Earlier SVR12 data were presented at the 2012 Conference
on Retroviruses and Opportunistic Infections in March 2012.
had two parts. Part A included 13 co-infected participants with CD4 cell counts
of at least 500 cells/mm3 who were not yet taking antiretroviral
therapy, as recommended by antiretroviral treatment guidelines in effect at the
included 47 co-infected people on antiretroviral treatment with stable HIV
suppression (HIV RNA <50 copies/ml). On the basis of prior drug-drug
interaction studies, they could be taking either efavirenz (Sustiva or Stocrin) plus tenofovir/emtricitabine (the drugs in Truvada) or ritonavir-boosted atazanavir
(Reyataz), plus either lamivudine (Epivir) or emtricitabine.
participants (nearly 90%) were men and the average age was about 45 years. Part
A included a higher proportion of people
of African descent (a group that does not respond as well to interferon-based
therapy). Overall, about
70% had the more challenging HCV genotype 1a (the rest had 1b) and just over
10% had advanced liver fibrosis or cirrhosis at baseline, though these factors
varied widely across treatment arms. Median CD4 cell counts in Part A and B
were approximately 600 and 500 cells/mm3, respectively.
in both parts of the study were randomly assigned to receive either telaprevir
or placebo in combination with 180mcg per week pegylated interferon alfa-2a (Pegasys) plus ribavirin (mostly
an 800mg per day fixed dose). People assigned to atazanavir took the usual 750mg three-times-daily
telaprevir dose. To compensate for a known drug-drug interaction that lowers
telaprevir levels, those taking efavirenz increased their dose to 1125mg thrice daily.
monoinfected people take telaprevir for variable lengths of time, according to
a response-guided therapy algorithm, all co-infected participants in this study
received triple therapy for 12 weeks followed by pegylated interferon/ribavirin
alone for 36 more weeks.
stopped treatment based on futility rules if they had HCV RNA greater than 1000
IU/mL or less than a 2 log10 decrease from baseline at week 12, or
detectable HCV viral load at week 24 or 36, or if they experienced HCV
Overall, 74% of participants taking
telaprevir triple therapy achieved SVR24 – or continued undetectable HCV RNA
at 24 weeks after completing treatment – compared with just 45% of those
taking pegylated interferon/ribavirin alone.
Among participants not taking antiretroviral
therapy in Part A, SVR24 rates were 71 and 33%, respectively. In Part B, 69%
of people using efavirenz and 80% of those using boosted atazanavir achieved
SVR24 with telaprevir, compared with 50% for both antiretroviral regimens with
pegylated interferon/ribavirin alone.
All these SVR24 rates were the same as
the SVR12 rates reported previously, confirming that SVR12 is an accurate
indicator of a cure.
Among the ten telaprevir recipients
who did not achieve SVR, two (5%) discontinued due to stopping rules, one (3%)
experienced post-treatment viral relapse, three (8%) had detectable HCV RNA at
the end of treatment and four (11%) were lost to follow-up.
Overall, people taking telaprevir
experienced more side-effects than those on pegylated interferon/ribavirin
alone. Three people (8%) taking telaprevir, but none in the placebo group,
discontinued treatment early due to adverse events.
Side-effects that occurred at least
10% more often among telaprevir recipients than among placebo recipients during
the twelve weeks on triple therapy included pruritis (34 vs 5%), headache (34
vs 23%), nausea (32 vs 18%), skin rash (29 vs 18%) and dizziness (21 vs 9%).
Myalgia, or muscle aches, was more common in the placebo arm (13 vs 23%). No one
in either arm experienced severe rash.
Anaemia of any severity was equally
common in both groups, at 18%. Whilst fewer telaprevir recipients had severe anaemia
(3 vs 5%), they were more likely to receive blood transfusions (11 vs 5%) and
erythropoietin-stimulating agents (8 vs 5%) to manage it.
No participants in either treatment arm
experienced HIV breakthrough. Absolute CD4 counts fell in both arms – a known side-effect
of interferon – but CD4 cell percentages did not change. Measured telaprevir
concentrations were similar for people on ART and those not being treated for
"Higher SVR24 rates were observed
in chronic genotype 1 HCV/HIV co-infected patients treated with telaprevir
combination treatment," the researchers concluded. "Drug interactions
with telaprevir and select [antiretrovirals] were not clinically meaningful. Overall
safety and tolerability profile of [telaprevir/pegylated interferon/ribavirin]
was comparable to that previously observed in HCV monoinfected patients".
"In the UK almost 9% of HIV positive
individuals are co-infected with hepatitis C," Mark Nelson,
Director of HIV Services at the Chelsea and Westminster Hospital, London, said in a Janssen
press release. "For this patient
group, new effective treatment regimens are particularly important due to their
higher risk of developing liver complications compared to mono-infected