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and Hepatitis.com Coverage of the
18th Conference on Retroviruses and
Opportunistic Infections (CROI 2011)
February 27 - March 2, 2011, Boston, MA
Telaprevir Improves Treatment Outcomes for HIV/HCV Coinfected People
HIV positive people coinfected with HCV tend to experience more rapid liver disease progression than individuals with hepatitis C alone. Furthermore, some studies -- though not all -- suggest that HIV/HCV coinfected patients do not respond as well to standard therapy consisting of pegylated interferon plus ribavirin.
Mark Sulkowski from Johns Hopkins University and colleagues reported interim results from Study 110, a Phase 2 clinical trial comparing telaprevir vs placebo combined with standard therapy in HIV/HCV coinfected participants not previously treated for chronic hepatitis C.
The study was divided into 2 parts. Part A included 13 coinfected patients with CD4 T-cell counts >500 cells/mm3 who were not yet taking antiretroviral therapy (ART) but had HIV viral loads <100,000 copies/mL. Part B included 46 coinfected patients with CD4 counts >300 cells/mm3 and undetectable HIV RNA (< 50 copies/mL) on 1 of 2 ART regimens:
As described in another CROI presentation, pharmacokinetic studies of healthy HIV and HCV negative volunteers showed that telaprevir has modest drug-drug interactions with several antiretroviral agents including lopinavir/ritonavir (Kaletra), darunavir (Prezista), and fosamprenavir (Lexiva). Based on these findings, efavirenz (Sustiva) and atazanavir were judged to be the most suitable HIV drugs for use with telaprevir. Efavirenz lowers telaprevir blood levels, but raising the telaprevir dose can compensate for this effect. No dose adjustment was considered necessary with atazanavir.
In both parts of the study participants who were randomly assigned to the active drug arm received telaprevir 3 times daily plus 180 mcg/week pegyalted interferon alpha 2a (Pegasys) plus either 800 mg/day or weight-based ribavirin for 12 weeks, followed by pegyalted interferon/ribavirin alone through week 48. Patients taking atazanavir received the usual 750 mg telaprevir dose, while those on efavirenz received a higher 1125 mg dose. People assigned to the control arm received standard-of-care therapy using pegyalted interferon/ribavirin for 48 weeks, with a placebo substituting for telaprevir during the first 12 weeks.
Most study participants were men, with an average age of 46 years. More than half of patients in Part A were black (a population that does not respond as well to interferon-based therapy), but this fell to less than one-third in Part B. Most patients had high HCV viral load and about 10% had bridging fibrosis or cirrhosis, 2 other predictors of poor treatment response.
"In this interim analysis, substantially more patients receiving a telaprevir-based regimen achieved undetectable HCV RNA at weeks 4 and 12," the investigators concluded. "The safety and tolerability of [telaprevir plus pegylated interferon/ribavirin] was consistent with that previously observed in HCV monoinfected patients; no novel adverse events were detected."
Follow-up will continue through 24 weeks after the end of treatment to determine sustained virological response (SVR) rates. In telaprevir studies of HCV monoinfected patients, RVR and cEVR were strong predictors of SVR.
In response to a question about the somewhat lower response rates at weeks 4 and 12 among atazanavir recipients compared with efavirenz recipients, Sulkowski said it was not possible to make conclusions about how ART choice might affect telaprevir efficacy based on the small numbers in this study.
After Sulkowski summarized these finings at a press conference following his presentation, fellow speaker Joseph Eron form the University of North Carolina said that given the data so far, he would only feel comfortable giving telaprevir in combination with atazanavir or efavirenz. Sulkowski concurred, adding that more studies of telaprevir/antiretroviral drug interactions are needed.
At the same press conference, Stefan Zeuzem from University Hospital in Frankfurt gave a brief recap of his Wednesday morning plenary talk on new antiviral therapies for management of HCV.
The impending approval of the first 2 direct-acting HCV agents -- telaprevir and boceprevir -- is a boon not only for the fields of infectious disease and hepatology, but for medicine as a whole, Zeuzem said. "30% more cure in a difficult-to-treat disease is a major achievement," he noted.
Zeuzem added that he expects 1-2 new anti-HCV drugs to be approved per year until 2015. "By the end of the decade we may well see an all oral regimen," he said. "That's what I want to achieve before retirement."
He cautioned, however, that a major education effort will be needed to help gastroenterologists and hepatologists use these new medications correctly, as they are less familiar with the lessons learned in the HIV field about drug combination, resistance, and adherence.
M Sulkowski, D Dieterich, K Sherman M, and others. Interim Analysis of a Phase 2a Double-blind Study of TVR in Combination with pegIFN-a2a and RBV in HIV/HCV Co-infected Patients. 18th Conference on Retroviruses and Opportunistic Infections. Boston. February 27-March 2, 2011. Abstract 146LB.
R van Heeswijk, A Vandevoorde, G Boogaerts, and others. Pharmacokinetic Interactions between ARV Agents and the Investigational HCV Protease Inhibitor TVR in Healthy Volunteers. 18th Conference on Retroviruses and Opportunistic Infections. Boston. February 27-March 2, 2011. Abstract 119.
S Zeuzem. New Antiviral Therapies in the Management of HCV (plenary). 18th Conference on Retroviruses and Opportunistic Infections. Boston. February 27-March 2, 2011.