Investigation of antiviral activity of 1-beta-D-arabinofuranosylthymine (ara-T) and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-ara-U) in monkeys infected with simian varicella virus.

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.