POTENTIAL FOR COMBINED THERAPY WITH 348U87, A RIBONUCLEOTIDE REDUCTASE INHIBITOR, AND ACYCLOVIR AS TREATMENT FOR ACYCLOVIR-RESISTANT HERPES-SIMPLEX VIRUS-INFECTION

Inhibitors of the ribonucleotide reductase of herpes simplex viruses ( HSV) potentiate the activity of acyclovir in vitro and in animal studi es. In addition, the combination of the ribonucleotide reductase inhib itor 348U87 and acyclovir has synergistic therapeutic effects against infections in mice due to thymidine kinase-deficient, thymidine kinase -altered, and DNA polymerase mutants of HSV. We performed a pilot stud y of topical combination therapy with 348U87 (3%) and acyclovir (5%) c ream for acyclovir-resistant, anogenital HSV infections in ten human i mmunodeficiency virus (HIV)-infected patients. Our results, with lack of complete reepitheliazation of lesions in all patients and poor viro logic response, suggest that this therapy is unlikely to be useful for this indication. (C) 1993 Wiley-Liss, Inc.