International News

June 3, 2007
Internal Medicine World Report, June 2006, Volume 0, Issue 0

Adefovir Dipivoxil Prevents Graft Reinfection in Patients with Chronic Hepatitis B

VIENNA—The use of the antiviral drug adefovir dipivoxil (Hepsera; ADV) to treat recurrent chronic hepatitis B virus (HBV) infection before and after a liver transplant prevents infection of the transplanted organ, investigators announced at the 41st Annual Meeting of the European Association for the Study of the Liver.

Eugene R. Schiff, MD, of the University of Miami, Florida, reported the results from 57 patients with lamivudine (Epivir)-resistant disease who received ADV in addition to lamivudine before and after transplantation.

No patient had evidence of HBV on either serologic or virologic testing during the 36 weeks of posttransplantation follow-up.

“Although the antiviral drug lamivudine may help prevent graft reinfection, resistance to lamivudine frequently develops, which increases a patient’s risk of morbidity and mortality,” Dr Schiff observed. “Our results demonstrate that ADV treatment helps manage the clinically challenging problem of lamivudine resistance and is therefore an important treatment for patients with lamivudine-resistant disease before and after transplantation.”

He emphasized that ADV was effective in patients regardless of concurrent use of hepatitis B immune globulin. “Hepatitis B immune globulin is frequently given along with lamivudine to help prevent reinfection; however, it is expensive and has to be given parenterally,” Dr Schiff said. “Our data suggest that perhaps these patients don’t need immune globulin as long as they are receiving both ADV and lamivudine.”

Oral PI/Pegylated Interferon Combo Shows Dramatic Benefits for Chronic HCV

VIENNA—The investigational oral protease inhibitor (PI) VX-950 (Vertex Pharmaceuticals), dosed in combination with pegylated interferon alfa-2a (Pegasys; peg-IFN), provides rapid and dramatic antiviral activity in patients with chronic hepatitis C virus (HCV) infection genotype 1 and is well tolerated, investigators announced at the European Association for the Study of the Liver meeting.

“With an increasing number of patients with HCV seeking treatment as their disease progresses, there is an urgent need for improved therapies,” Henk W. Reesink, MD, of the Academic Medical Center, Amsterdam, the Netherlands, pointed out. “This is particularly true for the chronic HCV patients with genotype 1 virus strain, which is the most common strain of hepatitis and historically the most difficult to treat.” He noted that “only about one half of patients improve with the current treatment standard, which involves a combination of weekly peg-IFN injections and twice-daily treatment with the antiviral agent ribavirin [Copegus]. Such treatment can cause debilitating side effects, which may decrease compliance, leading to treatment failure.”

Dr Reesink described results in 20 treatment-naïve patients who received oral PI VX-950 at a dose of 750 mg every 8 hours in combination with a standard dose of peg-IFN; the same dose of the PI alone; or a standard dose of peg-IFN alone.

The combination of the oral PI plus peg-IFN had the most potent antiviral activity, with a median viral load reduction of 5.5 log10 IU/mL after 14 days. “This is equivalent to a 300,000-fold decrease in viral levels,” Dr Reesink said.

All patients completed therapy, and no serious adverse effects were reported.

At the end of the trial, all 8 patients in the combination group opted to receive a full course of peg-IFN and ribavirin. Analysis at 3 months showed no evidence of viral rebound.

“The introduction of more effective therapies that may be given for a shorter treatment duration may mean that doctors will be more likely to treat chronic HCV patients with the genotype 1 strain as soon as they are diagnosed,” Dr Reesink said. “Given the length of treatment and the debilitating side effects of current therapies, physicians are sometimes reluctant to prescribe standard treatment, particularly if the patient has few or no signs of liver damage.”

Phase 3 Trial for H5N1 Vaccine Enlists 5 Large Spanish Hospitals

SPAIN—Five large national hospitals in Spain will participate in the first study of an H5N1 influenza vaccine (GlaxoSmithKline) to assess its side effects and immunogenicity in individuals aged >18 years. The study is expected to have 5052 participants from 7 countries (ie, Spain, Germany, Holland, Sweden, Russia, France, and Estonia), including 1500 from Spain. Participants will be randomized into 2 groups: 75% will receive 2 doses of the H5N1 influenza vaccine, and 25% will receive a dose of a conventional influenza vaccine and a placebo. The second dose will be administered 21 days after the first medical examination. Blood tests will be conducted in 10% of the participants to analyze the immune response triggered by the vaccine. Participants will record their side effects in the week after each dose is administered.