EVALUATION OF HPMPC THERAPY FOR PRIMARY AND RECURRENT GENITAL HERPES IN MICE AND GUINEA-PIGS

The nucleoside analogue S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cyto sine (HPMPC) inhibited the replication of herpes simplex virus (HSV) t ypes 1 and 2 in tissue culture cells at about 1.0 mug/ml, whereas Acyc lovir (ACV) had an EC50 of about 0.10-0.50 mug/ml. The purpose of thes e studies was to evaluate the efficacy of topically applied HPMPC in a nimal models of primary and recurrent genital HSV-2 infections. Mice t reated with 5%, 1% or 0.5% HPMPC three times daily, beginning 6 or 24 h after virus inoculation had reduced vaginal viral replication regard less of time of initiation of therapy. ACV at 5% also reduced vaginal viral replication, but not as effectively as HPMPC. In primary infecti on of guinea pigs, therapy with 5% or 1% HPMPC beginning at 24 h but n ot 72 h significantly altered lesion development. However, 5% HPMPC wa s highly toxic to guinea pigs. Vaginal viral replication was reduced s ignificantly with either 1% or 0.3% HPMPC initiated at 24 h. In these studies, HPMPC was also more efficacious than 5% ACV. Topical treatmen t with 1% HPMPC did not reduce the incidence or severity of spontaneou s or UV-induced recurrent genital lesions. These results indicate that topical therapy with 1%, 0.5% or 0.3% HPMPC was more effective than 5 % ACV in the treatment of primary genital HSV-2 infections of guinea p igs and mice and suggest that HPMPC should be considered for topical u se in humans.