CROI 2012: Early Data Show Drugs Effective in HCV Plus HIV

By Michael Smith, North American Correspondent, MedPage Today

Published: March 07, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

SEATTLE -- Two new drugs that directly target hepatitis C are effective in people also infected with HIV, researchers reported here.

Action Points

• These studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Explain that two different phase II trials found that sustained virologic response to hepatitis C virus (HCV) was achieved in more HCV/HIV coinfected patients treated with either boceprevir or telaprevir added to the cominbation of pegylated interferon plus ribavirin, as opposed to standard anti-HCV therapy alone.
• Note that results in both trials were comparable to treatment with these new drugs in patients infected with HCV alone, and the side effect profile was not different.

In separate phase II trials, the drugs -- telaprevir (Incivek) and boceprevir (Victrelis) -- each individually combined with standard hepatitis C therapy, showed about a 30% improvement in cure rates over standard therapy alone.

Despite the early stage of the research, the findings, reported at the annual Conference on Retroviruses and Opportunistic Infections, got an enthusiastic reception.

There's a clear "gap between the enthusiasm and the provisional nature of the data," commented David Thomas, MD, of Johns Hopkins University, who was not part of the studies but who chaired a press conference at which details were presented.

But he told MedPage Today there are two reasons for that: clinicians are feeling a sense of urgency about treating patients with HIV and hepatitis C, and "more substantive data" will not be available for a year and a half, when phase III trials begin to report.

"Cure matters," he said. "Here we are able to cure hepatitis C and we've never had that before in patients with HIV."

"There's 30% more people being cured," Thomas said. "That's a big deal."

Both drugs have been approved for treatment of hepatitis C in mono-infected patients, but not yet for people coinfected with HIV.

Both studies combined the novel drug with standard therapy – pegylated interferon and ribavirin -- and compared the results with standard therapy alone. Patients were allowed to keep taking their anti-retroviral medication. For this analysis, a cure was defined as a sustained virologic response – no detectable hepatitis C RNA -- 12 weeks after the end of treatment, the so-called SVR12.

For telaprevir, an intention-to-treat analysis of 60 patients showed that 74% of those in the telaprevir arm had an SVR12, compared with 45% of those on the standard therapy alone, according to Douglas Dieterich, MD, of Mt. Sinai School of Medicine in New York City.

He described the findings as a "huge leap forward" for treatment of coinfected people.

For boceprevir, the absolute numbers were not quite as robust, but the difference between the arms was similar, reported Mark Sulkowski, MD, of Johns Hopkins University School of Medicine.

In 98 patients, 60.7% of those taking boceprevir combined with standard therapy had an SVR12, compared with 26.5% of those getting standard therapy alone, Sulkowski reported.

In both studies, more than 80% of patients had hepatitis C RNA >800,000 IU/mL, and all had undetectable HIV levels before therapy for hepatitis C was added.

The differences between the arms in the two studies were 29% and 34.2%, respectively.

The findings are "shockingly comparable," Dieterich said.

Both Dieterich and Sulkowski suggested there is a pent-up desire to use the drugs in patients, even before phase III data are available and approval is forthcoming.

Until better data are available, "what should patients do?" asked Sulkowski. "These phase II trials, albeit small in size, demonstrate significant improvement over peginterferon and ribavirin."

"If you need to treat people, you need to treat people now," Dieterich said.

Both researchers said there is not a great deal of difference between outcomes for people with both viruses and those previously seen for patients with hepatitis C alone.

And although there are some interactions between the drugs and anti-retrovirals, there was little evidence that HIV might escape control. For instance, Sulkowski said, HIV viral breakthrough occurred in three of 64 patients on boceprevir and four of 34 on standard therapy alone.

Dieterich noted that the interferon part of the regimen "covers our back here" since it is itself a mild anti-retroviral. So, even if drug interactions lower the efficacy of the anti-retroviral medications, the interferon might pick up the slack.

"The real issue is going to come when we do away with interferon," as many clinicians hope can be done, he added.

The boceprevir study was supported by Merck. Sulkowski reported financial links with Merck and Vertex.

The telaprevir study was supported by Vertex. Dieterich reported financial links with Bristol Myers Squibb, Gilead, Idenix, Merck, Pharmasset, and Vertex.

Thomas reported financial links with Gilead and Merck.

Primary source: Conference on Retroviruses and Opportunistic Infections
Source reference:
Sulkowski M, et al "Boceprevir + pegylated interferon + ribavirin for the treatment of HCV/HIV-co-infected patients: End of treatment (week-48) Interim results" CROI 2012; Abstract 47.

Additional source: Conference on Retroviruses and Opportunistic Infections
Source reference:
Dieterich D, et al "Telaprevir in combination with pegylated interferon-a-2a+RBV in HCV/HIV-co-infected patients: A 24-week treatment interim analysis" CROI 2012; Abstract 46.

Source

Also See:

1. CROI 2012: Results from Investigational Studies with VICTRELIS™ (boceprevir) Presented at the Conference on Retroviruses and Opportunistic Infections to Understand Potential Use in Patients Coinfected with Chronic Hepatitis C and HIV-1
2. CROI 2012: Data from Phase 2 Study of an INCIVEK® Combination Regimen Showed 74% of People Co-Infected with Hepatitis C and HIV Had Undetectable Hepatitis C Virus 12 Weeks After Treatment Ended (SVR12)