penciclovir and Hepatitis-B--Chronic

Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M(2) inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.

Topics: Acyclovir; Adenine; Amantadine; Antiviral Agents; Comorbidity; Drug Therapy, Combination; Foscarnet; Ganciclovir; Guanine; Hepatitis; Hepatitis B, Chronic; Hepatitis C; Herpesviridae Infections; HIV Infections; Humans; Influenza, Human; Interferons; Lamivudine; Nucleosides; Oligopeptides; Organophosphonates; Oseltamivir; Proline; Protease Inhibitors; Pyrimidinones; Ribavirin; Telbivudine; Thymidine; Valacyclovir; Valganciclovir; Valine; Virus Replication; Zanamivir

After several nucleoside analogues have been tested against chronic hepatitis B virus (HBV) infection with minimal success, lamivudine seems to be a highly effective new therapeutic option. This review focuses on nucleoside metabolism and on the molecular action of lamivudine as well as on results of clinical studies for several indications. We report on results of trials on the use of lamivudine for chronic HBV infection, chronic HBV under immunosuppression and prophylaxis or treatment of HBV reinfection before or after orthotopic liver transplantation. Aspects of combination therapy of different nucleoside analogues as well as on combination of lamivudine with interferon are also highlighted. Although lamivudine seems to be highly effective in most patients at the start of therapy, development of resistance by mutations in the viral polymerase is a significant clinical problem. The mode of resistance development is compared with the situation in HIV infection. Possible cross-resistance with other nucleoside analogues and the perspectives of lamivudine therapy are also considered.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Drug Therapy, Combination; Famciclovir; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Immunocompromised Host; Interferons; Lamivudine; Liver Transplantation; Mutation; Nucleosides; Reverse Transcriptase Inhibitors