Acyclovir in Oral and Ganglionic Herpes Simplex Virus Infections

Abstract

The local and trigeminal ganglionic therapeutic efficacy of two topical and systemic antiviral drugs was studied in mouse lips inoculated with herpes simplex virus type 1 after thermal injury. Application of topical 3% acylovir (acycloguanosine) ointment three times daily for four days completely blocked the replication of virus in the lips, and the healing process was greatly accelerated compared with that in placebo-treated infected controls. However, neither the healing process nor the viral replication was influenced by similar therapy with 3% vidarabine ointment. When given systemically for four days, starting one day after inoculation, acyclovir (40-60 mg/kg per day) and vidarabine (50 mg/kg per day) significantly reduced the clinical manifestations on the lips and viral titers of cultures obtained from the lips. Establishment of viral latency in the trigeminal ganglion was significnatly inhibited by systemic acyclovir (60 mg/kg per day), whereas systemic vidarabine (50 mg/kg per day) was ineffective. These data suggest that acyclovir may be one of the most promising antiviral agents for the management of oral herpes viral infections and trigeminal ganglionic latency of virus as demonstrated in the mouse model.

Herpes Simplex Virus Type 2 Establishes Latency in the Mouse Footpad

“…It is well documented that established latent HSV infections in DRG are not eradicated by treatment with ACG (Field et al, 1979;Klein et al, 1979;Blyth et al, 1980). ACG treatment prevents or reduces the establishment of latency only when given during the acute infection (Field et al, 1979;Klein et al, 1979;Park et al, 1979). There remained the possibility of selective survival and establishment of ACGresistant virus in the mice during the course of the ACG treatment.…”

Penetration of guinea pig skin by acyclovir in different vehicles and correlation with the efficacy of topical therapy of experimental cutaneous herpes simplex virus infection

“…Topical ACV-PEG may have succeeded in these studies because the inoculation process altered the integrity of the stratum corneum or alternate routes of absorption were available, so that the ability of the formulation to penetrate stratum corneum was not a critical determinant of the outcome. For example, inoculation in several mouse models was achieved by needle scratches (9,12) or by thermal injury with a surgical cautery (17), procedures which are likely to have abrogated the barrier properties of the skin. In the guinea pig genital model, ACV may have achieved significant systemic levels by absorption across the introital or vaginal mucosa (11).…”

Effect of acyclovir and interferon on human hematopoietic progenitor cells

“…ACV inhibits herpes simplex virus types I and II and varicella-zoster virus at concentrations that have little effect on the division of mammalian fibroblasts (1,4,6,19,24) or lymphocytes (25). In mice, rabbits, and guinea pigs infected with herpes simplex virus types I and II ACV is both effective and nontoxic (7,12,20,24). The favorable therapeutic effect of ACV is explained by its efficient phosphorylation to an active form by cells which contain virusspecified kinases (6, 8) and the high affinity of herpesvirus-specified DNA polymerase for this active ACV triphosphate (6).…”