Effect of Phosphonoformate on Symptomatic Genital Herpes Simplex Virus Type 2 Infection of Guinea Pigs

Abstract

Using a guinea pig model of genital herpes simplex virus (HSV) type 2 infection, phosphonoformate treatment initiated after the onset of symptoms had a therapeutic effect on the outcome of disease. Severity of disease, viral shedding, and HSV-induced cellular changes in vaginal cytology were significantly reduced in drug-treated animals as compared to sham-treated animals, although virus was readily detected in the nervous system of animals from both groups. The percentage of animals harboring latent virus in their dorsal root ganglia was approximately the same in both drug-treated and sham-treated animals. No drug toxicity was found.

Treatment of primary acute genital herpes in guinea pigs by intraperitoneal administration of fluoropyrimidines

“…Concentrations of Na+, K+, lactate dehydrogenase, and glucose in the sera of untreated, diluent-treated, and drug-treated animals were all within normal limits, with the exception of slightly elevated serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase levels. These slightly elevated levels in all but untreated guinea pigs are consistent with alcohol intake (contained in the diluent) for 3 days before serum collection (data not shown) but were not noted in ACV-or PFA-treated guinea pigs in separate studies (7,10). No difference in lesion scores was noted between diluent-and saline-treated animals and controls.…”

“…Effective ACV and phosphonoformic acid (PFA) treatment of genital herpes in guinea pigs is well documented (1,4,6,10 laboratory (6, 10, 22) and is comparable to those used in other studies (8,14).…”

“…Effective ACV and phosphonoformic acid (PFA) treatment of genital herpes in guinea pigs is well documented (1,4,6,10). This model has also been used to show the potential of prophylactic therapy with a lipid amine (22), minimal effect of treatment with adenine arabinoside and several of its analogs (12), and failure of treatment with 2-deoxy-D-glucose (5,15 to inhibition by bromovinyldeoxyuridine (9), by its inability to induce an HSV-1-specific enzyme (21), and by neutralization with HSV-2-specific antisera.…”

“…Primary guinea pig embryo cells were prepared from 30-to 40-day-old Hartley guinea pig embryos (Camm Research Institute, Wayne, N.J.) as described previously (11 (6,10,22) and is comparable to those used in other studies (8,14 and FMAU on HSV replication. Since HSV-2 strain 1868 was was dissolved in water to yield a 2.5% solution and diluted in used in the animal studies described below, this virus strain saline.…”

“…ACV is a proven, effective antiviral agent and had become a standard for comparison with other antiviral agents. PFA is also an effective antiherpetic drug in both animal and human studies but has not been licensed for release in the United States (10,19). All It was noted that the lesion scores for untreated guinea pigs varied from experiment to experiment.…”