Jim Kling

March 08, 2012

March 8, 2012 (Seattle, Washington) — In 74% of patients coinfected with HIV and HCV, telaprevir led to undetectable levels of hepatitis C virus (HCV) RNA, according to the results of a study presented here at the 19th Conference on Retroviruses and Opportunistic Infections.

Response rates typically remain relatively low in coinfected patients, but telaprevir and other drugs in development are causing optimism among physicians and patients.

Douglas Dieterich, MD, professor of medicine at the Mount Sinai School of Medicine in New York City, reported the results of a 24-week interim analysis of a randomized double-blind placebo-controlled phase 2 trial of telaprevir in combination with pegylated interferon-alfa-2a (peg-IFN) and ribavirin.

In the study, 60 treatment-naïve HIV-positive patients with genotype 1 HCV were randomized into 1 of 2 groups: telaprevir 750 mg every 8 hours, peg-IFN 180 μg per week, and ribavirin 800 mg per day for 12 weeks, followed by 36 weeks of peg-IFN plus ribavirin (telaprevir group); or placebo and peg-IFN plus ribavirin for 48 weeks (control group).

Of this cohort, 47 patients also received stable predefined antiretroviral therapy (ART) with either efavirenz (16 in the telaprevir group; 8 in the control group) or atazanavir plus ritonavir (15 in the telaprevir group; 8 in the control group). Patients receiving efavirenz received telaprevir 1125 mg every 8 hours (instead of 750 mg). Thirteen patients did not receive any ART.

Mean patient age was 46 years, 88% were male, 27% were black, 68% had HCV subtype 1a, and 3.3% were diagnosed with cirrhosis.

At baseline, 92% of non-ART patients had HCV RNA levels of at least 800,000 IU/mL; 81% of ART patients exceeded that threshold.

For non-ART patients, mean CD4 count was 690 cells/mm3; for ART patients, it was 562 cells/mm3.

At week 12, HCV RNA was undetectable in 74% of patients in the telaprevir group and in 45% in the control group. Fewer patients in the telaprevir group than in the control group relapsed (3% vs 15%).

HCV viral breakthrough occurred in 3 patients in the telaprevir group. There were no HIV viral breakthroughs in any patients.

The frequency of abdominal pain, vomiting, nausea, pyrexia, dizziness, depression, and pruritus was at least 10% higher in the telaprevir group than in the control group.

Rates of bilirubin-related adverse events were more frequent in the atazanavir/ritonavir ART telaprevir group than in the corresponding control group (27% vs 0%).

Of patients receiving ART, 3 discontinued 1 or more study drugs because of an adverse event (cholelithiasis, jaundice, hemolytic anemia). The pharmacokinetics of telaprevir were similar with the 2 ART regimens, and were similar to those noted in previous didanosine studies in healthy volunteers.

The results show that "we need to treat people and need to treat them now. These patients are at risk for significant liver disease. They can't wait for these drugs to get approved," Dr. Dieterich said at a press conference.

The numbers are encouraging, he noted. "In the past, the response was anywhere from 30% to 50%. We've been waiting to have better drugs to treat coinfected individuals, because they develop cirrhoses and then require liver transplants. It's really important to see that telaprevir is safe and has a good response in our patients that desperately need to get rid of their hepatitis C to avoid further liver damage," Christopher Nguyen, MD, assistant clinical professor of medicine at the University of California at San Diego, and a primary care physician specializing in HIV treatment at the Tom Waddell Health Center in San Francisco, who attended the session, told Medscape Medical News.

Dr. Dieterich reports consulting and receiving research support from Bristol-Myers Squibb, Gilead Sciences, Merck, Pharmasset, and Vertex; and consulting and serving on the Data and Safety Monitoring Board for Idenix. Dr. Nguyen has disclosed no relevant financial relationships.

19th Conference on Retroviruses and Opportunistic Infections (CROI): Abstract 47. Presented March 6, 2012.

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