Adding telaprevir (Incivo or Incivek) to pegylated interferon and ribavirin shortens the duration of treatment and improves sustained response rates for HIV-positive men with acute hepatitis C virus (HCV) infection, according to a presentation yesterday at 'The Liver Meeting 2013', the 64th annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC.
Since the early 2000s, researchers have reported outbreaks of apparently sexually transmitted HCV infection among HIV-positive gay and bisexual men, first in the UK and continental Europe and later in Australia and the US.
Because acute hepatitis C is often asymptomatic or causes only non-specific flu-like symptoms, most people do not recognise and seek treatment when they acquire it. But people with HIV on antiretroviral therapy (ART) generally receive regular liver function tests to monitor for drug toxicity, and unexplained liver enzyme elevations may signal recent HCV infection.
Treating acute hepatitis C, rather than waiting until it becomes chronic (after six months), leads to high rates of sustained virological response (SVR), essentially doubling the cure rate in half the time (24 rather than 48 weeks for HCV genotype 1). However, people with HIV do not respond as well as HIV-negative individuals and they are more likely to need treatment as they less often spontaneously clear HCV.
Daniel Fierer from Mt Sinai Medical Center and fellow investigators with the New York Acute HCV Surveillance Network conducted a pilot study to evaluate whether adding the HCV protease inhibitor telaprevir to interferon-based therapy could increase the likelihood of sustained response and further shorten duration of treatment for acute hepatitis C in people with HIV.
This open-label study included 34 people consecutively enrolled at a single clinical practice between July 2011 and September 2012. Participants were sexually active HIV-positive men who have sex with men (MSM) with genotype 1 acute HCV infection, as indicated by new alanine aminotransferase (ALT) elevation or newly detectable HCV viraemia.
Participants in the study were first observed for several weeks to see if they would spontaneously clear HCV. Those who did not were treated with a triple regimen of 750mg three-times-daily telaprevir, 180mcg once-weekly pegylated interferon alfa-2a (Pegasys) and twice-daily weight-based ribavirin for 12 weeks, starting within six months of their first recorded ALT elevation.
If necessary, participants modified their antiretroviral regimen before starting hepatitis C treatment to replace agents known to interact with telaprevir. Permitted antiretrovirals included ritonavir-boosted atazanavir (Reyataz), raltegravir (Isentress), rilpivirine (Edurant) or efavirenz (Sustiva), all with tenofovir/emtricitabine (the drugs in Truvada).
Of the 34 men initially enrolled, seven could not receive telaprevir (due to HCV genotypes other than 1, lack of insurance coverage or other reasons) and were included in the comparator group, five people spontaneously cleared HCV before starting therapy and three declined treatment, leaving 19 men who started triple therapy.
Most of the treated participants (84%) were white and the median age was 44 years. All but two (89%) had the more difficult-to-treat HCV subtype 1a and 63% had the favourable IL28B 'CC' gene pattern associated with good interferon response.
A comparator group consisted of 48 HIV-positive MSM with genotype 1 acute hepatitis C who were treated with pegylated interferon and ribavirin alone between January 2008 and September 2012. This group was 58% white and the median age was 42 years; 90% had HCV 1a and 42% had the 'CC' gene variant.
At the end of treatment 16 out of 19 participants (84%) treated with triple therapy had undetectable HCV RNA. None of the men relapsed during post-treatment follow-up, yielding SVR12 and SVR24 rates of 84% as well.
Nearly half of participants changed antiretrovirals before starting hepatitis C treatment, and all maintained HIV viral suppression.
Two participants discontinued hepatitis C therapy, one due to herpes zoster and skin lesions and another due to interferon intolerance. Three people (16%) developed mild or moderate anaemia and had their ribavirin dose reduced. In addition, 18 people (95%) reported mild itching and two (11%) developed mild skin rash.
The SVR12 rate in the pegylated interferon/ribavirin comparator group was 63%, with 27% being partial or null responders and 10% experiencing post-treatment relapse.
Fierer also reported data from an additional 14 HIV-positive men treated with telaprevir triple therapy after the initial study ended, between October 2012 and October 2013. In this group, 71% were white, 93% had HCV subtype 1a and 36% had the 'CC' variant – closer to the proportion in the comparator group.
At the end of treatment, 93% had undetectable HCV RNA, and six out of seven men (86%) with sufficient follow-up achieved SVR12 – similar to the rate in the pilot study despite the lower proportion with favourable IL28B status. The one individual who experienced treatment failure stopped therapy at week 6. Again, there were no relapses among those who completed therapy.
Combining this group with the earlier patients treated with telaprevir, the overall SVR12 rate for triple therapy was 85%, which fell just short of a statistically significant difference from the 63% SVR12 rate in the standard therapy comparator group (p = 0.06).
Adding telaprevir to pegylated interferon improves cure rates and cuts treatment duration in half again, to 12 rather than 24 weeks, Fierer concluded. Triple therapy was well tolerated and study participants said they were pleased with the short course of treatment.
Fierer acknowledged that telaprevir is on the way out, given the pending approval of next-generation direct-acting antivirals such as sofosbuvir that are more effective, better tolerated and have less potential for interaction with HIV drugs.
But whatever regimen is used, he added, providing treatment now will prevent further HCV infections, and he strongly encouraging "thinking of treatment as prevention".
Fierer DS et al. Telaprevir in the treatment of acute HCV infection in HIV-infected men: SVR 12 results. 64th Annual Meeting of the American Association for the Study of Liver Diseases, Washington, DC, abstract 40, 2013.