The antiviral activity of 1-,3-n-arabinofuranosylcytosine (ara-C, cytarabine, Cytosar), 5-iodo-2'-deoxyuridine (IdUrd), 9-,8-D-arabinofuranosyladenine (ara-A), and disodium phosphonoacetate (PAA) have been compared in herpes simplex virus type 2 (HSV-2)-infected primary rabbit kidney cells and in female hamsters with genital HSV-2 infection. In vitro, ara-C and IdUrd were more active than ara-A, and PAA was least active. In female hamsters with genital HSV-2 infection, intravaginal treatment with PAA or ara-A was more effective than either ara-C or IdUrd. PAA was more active than ara-A when treatment was initiated early (1 h) after infection. The activity of PAA was greatly reduced if initiation of treatment was delayed for 24 h. Both PAA and ara-A reduced the virus titers of the vagina and protected hamsters from death when the drugs were given by either the intravaginal or subcutaneous route, with intravaginal treatment being more effective.Genital herpesvirus infections, primarily caused by herpes simplex virus type 2 (HSV-2), are transmitted by venereal contact (9, 26). The infection can be painful and recurrent. If lesions are present late during the gestation period, the neonate is at high risk, resulting in disease with high morbidity and mortality (25). Furthermore, HSV-2 has been implicated in the etiology of cervical carcinoma (2,4,23).At the present time, there is no effective treatment for genital HSV infections. However, several agents with antiherpes activity in other systems have been studied in herpes genitalis. Topical application of certain heterocyclic dyes, followed by exposure to light, has been proposed as a method for treating this disease (5). However, in subsequent studies with proflavine (34), or in a double-blind study with neutral red (24), it was not possible to demonstrate efficacy.We have recently described the experimental genital infection of female hamsters with HSV-2 (30). In the studies described herein, several drugs with reported antiherpes activity have been compared in vitro and in female hamsters with genital HSV-2 infection.
MATERIALS AND METHODSVirus. Stocks of HSV-2 (strain 35D) were supplied by L. T. Chien, University of Tennessee. The virus had a titer of 7.5 x 105 to 1.0 x 0l plaque-forming units per 0.5 ml on primary rabbit kidney monolayers.In vitro antiviral activity. Contiguous monolayers of primary rabbit kidney cells were infected by incubating 0.5 ml of stock virus with drained monolayers (60-mm plastic petri dishes, Falcon) for 60 min at 370C. The monolayers were washed and refed with 4.5 ml of Eagle medium containing 3% fetal bovine serum. The drugs were prepared in Hanks solution, and 0.5 ml of the appropriate dilution was added to each plate, resulting in the concentrations indicated. The cultures were harvested to -70°C when approximately 50 to 75% of the cells in the control cultures showed evidence of cytopathology. The virus titers of the frozen-thawed cultures were determined by the plaque method on rabbit kidney monolayers.Genital infection of femal...