sorivudine 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: 2-Aminopurine; Acyclovir; Antiviral Agents; Arabinofuranosyluracil; Chickenpox; Drug Resistance, Microbial; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Valacyclovir; Valine

The antiviral and clinical efficacy of sorivudine in adults with varicella was evaluated in a double-blind, placebo-controlled randomized trial. A total of 186 patients were hospitalized for isolation and treatment within 96 h of rash onset. The diagnosis of varicella was confirmed in 184 patients with paired sera. Patients were randomly assigned to receive 10 or 40 mg of sorivudine or an identical placebo once a day for 5 days. Treatment with 40 mg of sorivudine (compared with placebo) shortened the mean time to 100% crusting from 6.6 to 5.8 days (P = .004) and reduced the mean days that new lesion formed from 3.9 to 3.1 (P = .014). Mean days of cutaneous viral shedding were reduced from 3.3 in the placebo group to 2.6 in the 40-mg sorivudine group (P = .002). The effectiveness of therapy was not affected by the duration of rash before initiation of therapy. Sorivudine is a promising new agent for the treatment of varicella-zoster virus infections.

Topics: Administration, Oral; Adult; Antiviral Agents; Arabinofuranosyluracil; Chickenpox; Cohort Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Herpesvirus 3, Human; Hospitals, Military; Humans; Immunocompetence; Male; Placebos; Polymerase Chain Reaction; Skin

The polymerase chain reaction (PCR) was used to detect varicella-zoster virus (VZV) DNA in respiratory epithelial cells and in peripheral blood leukocytes from adults with varicella. VZV DNA was detected in oropharyngeal epithelium in 62% of patients early in the course of varicella; the amount of VZV DNA declined with time and was detectable in only 22% of patients for greater than 6 days. VZV DNA was also detected in peripheral blood leukocytes in 74% of patients early in disease and was detected in both polymorphonuclear and mononuclear leukocytes. PCR demonstrated the presence of VZV DNA in the oropharynx and blood of most patients during varicella, in contrast to the ability to detect VZV in these tissues by viral culture.

Topics: Adult; Antiviral Agents; Arabinofuranosyluracil; Base Sequence; Cells, Cultured; Chickenpox; DNA, Viral; Herpesvirus 3, Human; Humans; Male; Molecular Sequence Data; Oropharynx; Polymerase Chain Reaction

We evaluated the treatment of varicella-zoster infection with BV-araU in immuno-compromised patients with haematological malignancies in a randomized controlled study. Comparison was made between doses of 150 and 30 mg/day. For ethical reasons there was no placebo group. The percentage of patients given a 'very effective' rating by both attending physicians and the Evaluation Committee was significantly higher in the 150 mg/day group (56.0%) compared to the 30 mg/day group (15.0%). There was no significant difference in efficacy rate ('very effective' plus 'effective') between the two groups. The incidence of side effects was low (7.8%), all were mild and disappeared on stopping treatment. These results suggest that BV-araU is clinically useful, especially at a dose of 150 mg/day in immunocompromised patients. Further comparative studies between BV-araU and acyclovir or vidarabine are indicated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiviral Agents; Arabinofuranosyluracil; Chickenpox; Child; Hematologic Diseases; Herpesvirus 3, Human; Humans; Immune Tolerance; Middle Aged; Remission Induction

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Arabinofuranosyluracil; Chickenpox; Drug Resistance, Microbial; Female; Ganciclovir; Herpesvirus 3, Human; Humans; Retinal Necrosis Syndrome, Acute

Topics: Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Arabinofuranosyluracil; Chickenpox; Drug Resistance; Herpesvirus 3, Human; Humans; Male

BV-araU (1-beta-D-arabinofuranosyl-E-5-[2-bromovinyl]uracil) has potent antiviral activity against varicella zoster virus in cell culture and is undergoing clinical evaluation. In the present study, pharmacokinetic parameters and the efficacy of BV-araU against infection with simian varicella virus (SVV) were evaluated in African green monkeys. Pharmacokinetic parameters were determined by analysis of the BV-araU content of sera obtained after oral and intravenous administration to normal monkeys. Peak serum concentrations showed dose proportionality, with the 0.1 mg/kg dose resulting in a peak serum concentration of 0.05 micrograms/ml, the approximately ED50 value for the SVV inoculum in cell culture. BV-araU administered orally twice daily at 0.1 mg/kg for 10 days starting 48 h after intratracheal SVV infection prevented vesicular rash development and suppressed viremia. Effective therapy could be initiated 96 h after infection. Taken together, these results indicate that BV-araU is effective oral therapy at doses that achieve peak serum levels equivalent to the ED50 for SVV in cell culture.

Topics: Administration, Oral; Adsorption; Animals; Antiviral Agents; Arabinofuranosyluracil; Biological Availability; Cells, Cultured; Chickenpox; Chlorocebus aethiops; Dose-Response Relationship, Drug; Female; Herpesvirus 3, Human; Male

1-beta-D-Arabinofuranosylthymine (ara-T) and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-ara-U) were shown to have antiviral activity in vitro and in vivo against simian varicella virus. Both compounds successfully prevented clinical disease caused by inoculation of African green monkeys with simian varicella virus, eliminating the development of rash and substantially suppressing viremia. Ara-T treatment was effective by either intraperitoneal or oral routes of administration and BV-ara-U was active by both oral and intramuscular routes. Ara-T, however, was associated with the appearance of marked signs of neurotoxicity. Histologic examination of brain tissue demonstrated chromatolysis and pyknosis of neurons and pyknotic nuclei in glial cells. The neurologic impairment persisted in affected monkeys. This observation of central nervous system toxicity in monkeys is in contrast to studies in mice and rats where high doses of ara-T by multiple routes of administration were nontoxic. No apparent toxicity was observed in monkeys treated with BV-ara-U.

Topics: Animals; Arabinofuranosyluracil; Arabinonucleosides; Chickenpox; Chlorocebus aethiops; Herpesviridae Infections; Nervous System; Neurons; Thymidine; Uridine