acyclovir 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

The development of new antiviral strategies for the treatment of chronic hepatitis B remains a major goal since hepatitis virus (HBV) is resistant to interferon treatment as well as to new nucleoside analogs. HBV is a small DNA virus that replicates its genome via a reverse transcription step. The viral polymerase has been the main viral target that was studied to design new antiviral treatments. Active research has led to the discovery of new nucleoside analogs that are potent inhibitors of the viral reverse transcriptase. Among them, lamivudine has also proven antiviral efficacy in clinical trials with a sustained inhibition of viral replication. However, due to the kinetics of viral clearance, long-term antiviral therapy is necessary to eradicate viral infection. These prolonged regimens are associated with the emergence of drug-resistant strains that harbor mutations in the viral polymerase gene within the conserved B and C domains. New approaches using combinations of nucleoside analogs or other strategies, such as immune intervention (DNA vaccine, stimulation of the TH1 response ) or gene therapy (antisense oligonucleotides, dominant negative mutants), should therefore be evaluated in animal models to optimize the current antiviral protocols.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Clinical Trials as Topic; Drug Resistance, Microbial; Drug Therapy, Combination; Famciclovir; Hepatitis B, Chronic; Humans; Lamivudine; Virus Replication

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

The effect of ganciclovir prophylaxis on reinfection of hepatic allografts by hepatitis B virus (HBV) was studied in 26 patients undergoing orthotopic liver transplantation (OLT) for decompensated cirrhosis due to HBV. Patients were randomized to receive either ganciclovir (6 mg/kg/day intravenously for a total of 100 days) or acyclovir (10 mg/kg every 8 hours intravenously until discharged and then 800 mg orally every 6 hours) for a total of 100 days after OLT as part of a study of prophylaxis against cytomegalovirus infection. All patients received hepatitis B immunoglobulin (HBIG), 10,000 units intravenously, during the anhepatic phase, daily for the first 7 days, after OLT, and then every 4 weeks for 6 months, Seven of 12 (58%) patients in the ganciclovir group developed recurrent HBV, compared with 6/14 (46%) of the acyclovir group (nonsignificant). No significant difference was observed in time to recurrent HBV in the ganciclovir group (mean 13.2 months) compared to the acyclovir group (mean 11 months). Our results suggest that ganciclovir administered prophylactically for 100 days after OLT does not prevent or delay graft reinfection by HBV.

Topics: Acyclovir; Administration, Oral; Adult; Aged; Antiviral Agents; Base Sequence; Cytomegalovirus Infections; Drug Administration Schedule; Female; Ganciclovir; Graft Rejection; Graft Survival; Hepatitis B, Chronic; Humans; Infusions, Intravenous; Liver Transplantation; Male; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction; Survival Rate; Transplantation, Homologous; Treatment Failure

We report on a chronic asymptomatic hepatitis B surface antigen (HBsAg) carrier who developed an increase in aminotransferase and HBsAg levels 1 year after lung transplantation. During treatment for cutaneous herpes simplex virus (HSV) infection with oral valaciclovir there was a marked decrease in replicating hepatitis B virus (HBV)-DNA and aminotransferase levels, which was sustained for 9 months by continuing low-dose valaciclovir. A second rise in aminotransferase levels again responded to a valaciclovir dose increase and the HBV-DNA levels declined further. Although we cannot exclude a spontaneous variation of the serologic parameters, our observation suggests that valaciclovir may represent a valuable therapeutic option in the treatment of chronic hepatitis B after lung transplantation.

Topics: Acyclovir; Bronchiectasis; Carrier State; Chronic Disease; Female; Follow-Up Studies; Graft Survival; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Humans; Lung Transplantation; Middle Aged; Postoperative Complications; Preoperative Care; Risk Assessment; Serologic Tests; Treatment Outcome; Valacyclovir; Valine

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Injections, Intravenous; Injections, Subcutaneous; Interferon-alpha; Liver Function Tests; Middle Aged; Randomized Controlled Trials as Topic; Virus Replication