brivudine and Chickenpox

Antiviral treatment of herpesvirus infections is rapidly changing since the advent of new drugs with improved oral availability. The efficacy of valaciclovir, the prodrug of aciclovir, and famciclovir, the prodrug of penciclovir, in the treatment of herpes genitalis and acute herpes zoster has been well documented in large clinical trials. Both drugs are effective on zoster-associated pain. Brivudin and sorivudine which are the most active compounds against varicella-zoster virus (VZV) in cell culture have also been successful in the treatment of herpes zoster. Aciclovir is still the standard therapy of severe herpes simplex virus (HSV) and varicella virus infections. In patients treated with aciclovir, the mortality of herpes encephalitis has been reduced to about 25%. The development of resistance against aciclovir and the other nucleoside analogues has not been a problem to date in the treatment of immunocompetent individuals. However, in immunocompromised patients, aciclovir-resistant HSV strains often emerge. In such cases, intravenous foscarnet is the current treatment of choice.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Antiviral Agents; Arabinofuranosyluracil; Bromodeoxyuridine; Chickenpox; Drug Resistance, Microbial; Encephalitis, Viral; Famciclovir; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Humans; Immunocompromised Host; Prodrugs; Simplexvirus; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immune Tolerance; Interferon Type I; Interferons; Vidarabine

After a discussion of the principles of antiviral chemotherapy, treatment and chemoprophylaxis of the following virus infections are reviewed in detail: the various manifestations of herpes simplex virus infections, varicella-zoster, cytomegalovirus infections, Epstein-Barr virus infections, laryngeal papillomas, and influenza A. Special reference is made to the treatment of immunocompromized patients. Acycloguanosine (acyclovir) has been found particularly useful in the treatment of herpes simplex virus and varicella zoster virus infections in immunocompromized patients and for herpesencephalitis. Varicella-zoster can also be treated effectively with bromovinyldeoxyuridine (BVDU). Toxicity of the currently used antiviral drugs is discussed as well as the problem of drug resistance.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Child; Clinical Trials as Topic; Cytomegalovirus Infections; Double-Blind Method; Encephalitis; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Pemphigoid Gestationis; Pregnancy; Vidarabine; Virus Diseases

The alphaherpesvirus varicella-zoster virus (VZV) causes chickenpox and shingles. Current treatments are acyclovir (ACV) and its derivatives, foscarnet and brivudine (BVdU). Additional antiviral compounds with increased potency and specificity are needed to treat VZV, especially to treat post-herpetic neuralgia. We evaluated β-l-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)] uracil (l-BHDU, 1) and 5'-O-valyl-l-BHDU (2) in three models of VZV replication: primary human foreskin fibroblasts (HFFs), skin organ culture (SOC) and in SCID-Hu mice with skin xenografts. The efficacy of l-BHDU in vivo and its drug-drug interactions were previously not known. In HFFs, 200μM l-BHDU was noncytotoxic over 3days, and l-BHDU treatment reduced VZV genome copy number and cell to cell spread. The EC50 in HFFs for l-BHDU and valyl-l-BHDU were 0.22 and 0.03μM, respectively. However, l-BHDU antagonized the activity of ACV, BVdU and foscarnet in cultured cells. Given its similar structure to BVdU, we asked if l-BHDU, like BVdU, inhibits 5-fluorouracil catabolism. BALB/c mice were treated with 5-FU alone or in combination with l-BHDU or BVdU. l-BHDU did not interfere with 5-FU catabolism. In SCID-Hu mice implanted with human skin xenografts, l-BHDU and valyl-l-BHDU were superior to ACV and valacyclovir. The maximum concentration (Cmax) levels of l-BHDU were determined in mouse and human tissues at 2h after dosing, and comparison of concentration ratios of tissue to plasma indicated saturation of uptake at the highest dose. For the first time, an l-nucleoside analog, l-BHDU, was found to be effective and well tolerated in mice.

Topics: Acyclovir; Animals; Antiviral Agents; Bromodeoxyuridine; Cell Line; Chickenpox; Dioxolanes; Drug Therapy, Combination; Fluorouracil; Foscarnet; Herpes Zoster; Herpesvirus 3, Human; Humans; Mice; Mice, Inbred BALB C; Mice, SCID; Nucleosides; Organ Culture Techniques; Skin; Uracil; Virus Replication

Herpes zoster (HZ) is one of the most common complications after bone marrow transplantation (BMT) in children. Apart from treatment with antiviral drugs, effective prevention by active immunization with varicella-zoster virus (VZV) appears to be possible. In this study 15 patients were vaccinated with a live attenuated VZV vaccine (Varilrix) 12-23 months after BMT. The vaccine was well tolerated without adverse reactions. Chickenpox or HZ were not observed for up to 2 years after immunization. Eight out of nine seronegative patients seroconverted and in six virus-specific IgG could still be demonstrated 2 years later. The incidence of VZV diseases in 133 non-immunized children after BMT was 26.3%. Infections usually occurred within 18 months after BMT.

Topics: Adolescent; Antibodies, Viral; Antiviral Agents; Bone Marrow Transplantation; Bromodeoxyuridine; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; Dose-Response Relationship, Drug; Follow-Up Studies; Herpes Zoster; Humans; Immune Tolerance; Immunoglobulin G; Retrospective Studies; Vaccination

Topics: Aminopterin; Antiviral Agents; Bromodeoxyuridine; Cell Line; Chickenpox; DNA Replication; DNA-Directed DNA Polymerase; DNA, Viral; Drug Resistance, Microbial; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunoenzyme Techniques; In Vitro Techniques; Kinetics; Mutation; Thymidine Kinase; Viral Plaque Assay; Virus Replication

In the period June 1980-April 1983, 21 children with malignant disease were admitted because of an intercurrent varicella or zoster infection. They were treated with the new antiviral drug BVDU [(E)-5-(2-bromovinyl)-2'-deoxyuridine]. The drug was administered orally at a dose of 15 mg/kg per day for 5 days. All our patients responded promptly to BVDU treatment and recovered completely from their varicella or zoster infections without complications. No toxic side-effects due to the drug were observed.

Topics: Administration, Oral; Adolescent; Animals; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Child; Child, Preschool; Female; Herpes Zoster; Humans; Male; Neoplasms

For immunocompromised patients virus infections represent a definite risk, particularly infections with measles virus and viruses of the herpes group (primary infections or reactivations). Vidarabine, acyclovir and bromovinyldeoxyuridine are therapeutically active against varicella, zoster, and herpes simplex, provided they are administered early in the course of disease. For zoster at least, the efficacy of interferon has been documented in controlled studies. No convincing therapy is so far available for the severe cytomegalovirus infections. Interferons obtained with DNA recombinant techniques are of significant promise in the near future.

Topics: Acyclovir; Antiviral Agents; Bromodeoxyuridine; Chickenpox; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Humans; Immune System Diseases; Vidarabine; Virus Diseases