approved treatments for hepatitis B virus (HBV) infection include the immunomodulatory agent IFN-α and nucleos(t)ide analogues. (= 0.002) for hepatitis B e (HBe) antigen. Serum HBV DNA levels were below 400 copies/mL in 54% (= 167) of the emtricitabine group and only 2% (= 81) of the placebo group (< 0.001) while alanine aminotransferase levels were normal in 65% (109/167) of the emtricitabine group and 25% (20/81) of the control group (< 0.001). At wk 48 20 of 159 patients (13%) from the emtricitabine group in whom HBV DNA was detected at the end of treatment had virus with resistance mutations (95% confidence interval 8 The rate of seroconversion to anti-HBe (12%) and loss of HBe antigen were not different between arms and the safety profiles of emtricitabine and placebo were comparable during treatment. Forty-eight weeks of emtricitabine treatment resulted in significant histologic virologic and biochemical Nepicastat improvement in chronic Nepicastat HBV infected patients regardless of whether HBe antigen was detectable. Phase III clinical trials are underway to determine the long-term safety and efficacy of emtricitabine however its role as a monotherapy may be limited by its structural similarity to lamivudine and the corresponding risk of drug resistance. TENOFOVIR (VIREAD PMPA) Tenofovir was FDA approved in 2001 Nepicastat for use in HIV infected adults in combination with other antiretroviral agents. Lamivudine-associated and ADEFOVIR-resistant mutations were not detected when tenofovir was used in a clinical trial. Thus tenofovir may be a highly effective rescue drug in HBV-infected patients who show altered responsiveness to lamivudine and ADEFOVIR. An additional double-blind placebo-controlled trial showed that tenofovir may be a useful Rabbit monoclonal to IgG (H+L)(HRPO). component of antiretroviral therapy for HIV/HBV co-infected patients. Importantly tenofovir is equivalent to adefovir in its ability to reduce HBV DNA levels and may in fact be superior. If HBV treatment can be deferred until combination antiretroviral therapy for HIV contamination is needed the combination of tenofovir plus lamivudine or emtricitabine will be the potent HBV therapy and a solid backbone for HIV combination antiretroviral therapy and a potent treatment for HBV and it likely decreases the emergence of HBV resistance. It will decrease the chance that HBV resistance will emerge as well. CLEVUDINE (L-FMAU) Clevudine is a nucleoside analog with an unnatural beta-L configuration and studies suggest that it is effective against lamivudine-resistant HBV mutants. In the Woodchuck model a daily clevudine dose of 10 mg/kg resulted in a 100 million copies’ decrease in viral load. Interestingly a delayed rebound in viral load was observed after buy Nepicastat drug cessation in a dose-dependent manner. No evidence of clevudine toxicity was observed in Nepicastat treated animals however further studies are being conducted to assess its long-term efficacy and safety. Clinical trials show that clevudine is one of the most potent analogs available for treating HBV and that its antiviral effects can last up to 6 mo after treatment as illustrated by sustained normalization of ALT levels. The mechanism by which clevudine elicits its anti-hepadna virus activity is distinct from other nucleoside analogs. It acts as a competitive inhibitor by binding to the catalytic site of HBV polymerase and inhibiting the priming of HBV DNA chain elongation. Nucleoside inhibitors in general interfere with viral polymerase activity through Nepicastat competitive inhibition and incorporation into the viral DNA strands. TELBIVUDINE (LdT) Telbivudine is a novel nucleoside analog that is being developed for the oral treatment of chronic HBV. It is a highly specific and selective inhibitor of replication..