Back HIV/Hepatitis Coinfection CROI 2013: Adding Telaprevir Increases Acute Hepatitis C Cure Rate for HIV+ Men

Coinfection

CROI 2013: Adding Telaprevir Increases Acute Hepatitis C Cure Rate for HIV+ Men

alt

Adding telaprevir (Incivek) to pegylated interferon and ribavirin shortens the duration of therapy and improves the likelihood of a cure for HIV positive men with acute sexually transmitted hepatitis C virus (HCV), according to study findings presented at the 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013) last week in Atlanta.

Since the early 2000s researchers have been reporting outbreaks of apparently sexually transmitted hepatitis C virus (HCV) among HIV-positive gay and bisexual men, first in the U.K. and continental Europe and later in Australia and the U.S.

Acute hepatitis C often has no symptoms -- or common general symptoms like fever that can be mistaken for a 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 elevations of alanine aminotransferase (ALT) and other liver enzymes should trigger viral hepatitis testing, which may reveal recent infection.

It is well known that treating hepatitis C during acute or recent infection rather than waiting until the chronic phase (6 months after infection) is associated with high sustained response rates. In one key study of HCV 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 clear-cut, 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 coinfected people, but coinfected 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 eligible patients consecutively enrolled at a single clinical practice 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 (at least triple the usual level) 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 patients 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) with tenofovir/emtricitabine (the drugs in Truvada).

Within 6 months of their first noted ALT elevation, participants were started on a 12-week triple combination regimen of 750 mg (or 1125 mg if using efavirenz) thrice-daily oral telaprevir, 180 mcg once-weekly injected pegylated interferon 2a (Pegasys), and twice-daily weight-based oral ribavirin.

Of the 40 participants initially enrolled half were never treated; 7 had HCV genotypes other than 1 (the only one for which telaprevir is indicated), 5 did not have insurance that would cover telaprevir for this unapproved purpose, and 1 had unmanageable interactions with his ART regimen. In addition, 5 people spontaneously cleared HCV before starting therapy and 2 refused treatment.

Most (85%) of the 20 treated participants were white and the median age was 44 years; 18 had the more difficult-to-treat HCV subtype 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, but a majority of post-treatment relapses among patients taking direct-acting antiviral agents 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.

Results

  • 17 out of 20 patients (85%) had undetectable HCV RNA at the end of treatment and SVR4 at 4 weeks post-treatment.
  • Among 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.
  • 4 participants were treated for less than the full 12 weeks (ranging from 4 to 8 weeks) and all maintained HCV suppression (at weeks 4, 12, and 24) after stopping therapy.
  • 3 people were given a "tail" of pegylated interferon/ribavirin alone after finishing 12 week of triple therapy due to slow response or personal preference.
  • 3 people, all with unfavorable IL28B CT or TT patterns, experienced treatment failure, including 2 "null responders" who did not suppress viral load below 1000 IU/mL by week 4 (1 with HCV subtype 1a, 1 with 1b) and 1 person (subtype 1a) who experienced late viral breakthrough at week 12 of treatment.
  • Among the 9 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 2 developed skin rashes.
  • 1 person stopped treatment at week 4 due to anemia that required a blood transfusion, and 3 others reduced their ribavirin doses for this reason; 1 other participant stopped at week 5 due to interferon side effects.

Summarizing these results, Fierer said that 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, and most people who were excluded from treatment for one reason or other did not end up clearing the virus.

3/11/13

Reference

D Fierer. Telaprevir for Acute Hepatitis C Virus in HIV+ Men both Shortens Treatment and Improves Outcome. 20th Conference on Retroviruses and Opportunistic Infections. Atlanta, March 3-6, 2013. Abstract 156LB.