November 5, 2013

11/05/13

By: ELIZABETH MECHCATIE, Family Practice News Digital Network

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

emechcatie@frontlinemedcom.com

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Also See: Gilead Announces Phase 3 Results for an All-Oral, Sofosbuvir-Based Regimen for the Treatment of Hepatitis C in Patients Co-Infected With HIV

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