Tenofovir (Viread): Antiviral agent approved for the treatment of chronic hepatitis B in adults

New indication: Tenofovir (Viread), an antiviral agent, was approved on August 13, 2008, for the treatment of chronic hepatitis B in adults.

Tenofovir is an antiviral agent that inhibits the activity of hepatitis B virus (HBV) polymerase by competing with deoxyadenosine 5'-triphosphate and by DNA chain termination. Tenofovir was previously approved for use in combination with other antiretroviral agents for the treatment of HIV-1 infection; this agent was approved on August 13, 2008, for the treatment of chronic hepatitis B in adults.

Efficacy. The efficacy of tenofovir for the treatment of chronic hepatitis B was evaluated in 2 randomized, double-blind, active-controlled studies; Study 0102 enrolled hepatitis B e antigen-negative (HBeAg–) patients (N=375), and Study 0103 enrolled HBeAg+ patients (N=266). In both studies, patients were randomized to treatment with either tenofovir 300 mg or adefovir 10 mg for 48 weeks. The primary end point was complete response to treatment, defined as HBV DNA <400 copies/mL and Knodell necroinflammatory score improvement of ≥2 points without worsening in Knodell fibrosis. In Study 0102, 71% of tenofovir-treated patients demonstrated a complete response versus 49% of adefovir-treated patients, and in Study 0103, complete response was achieved by 67% of tenofovir-treated patients and 12% of adefovir-treated patients. In Study 0102, 93% of tenofovir-treated patients demonstrated HBV DNA <400 copies/mL versus 63% of adefovir-treated patients; in Study 0103, 76% of tenofovir-treated patients demonstrated HBV DNA <400 copies/mL versus 13% of adefovir-treated patients. A histologic response (Knodell necroinflammatory score improvement of ≥2 points without worsening in Knodell fibrosis) was achieved by 72% of tenofovir-treated patients and 69% of adefovir-treated patients in Study 0102 and by 74% of tenofovir-treated patients and 68% of adefovir-treated patients in Study 0103.

Safety. In patients treated with nucleoside analogues alone or in combination with other antiretroviral drugs, cases of lactic acidosis and severe hepatomegaly with steatosis have been reported; some of these cases have been fatal. Discontinuation of anti-HBV therapy can be associated with severe acute exacerbations of hepatitis infection. Therapy with tenofovir has been associated with renal impairment, including instances of acute renal failure and Fanconi syndrome. In patients infected with both HBV and HIV-1, tenofovir should be used only as part of an appropriate antiretroviral combination treatment regimen. The most common adverse events associated with tenofovir treatment include nausea, abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain, and skin rash.