HPMPC, A BROAD-SPECTRUM TOPICAL ANTIVIRAL AGENT, INHIBITS HERPES-SIMPLEX VIRUS TYPE-1 REPLICATION AND PROMOTES HEALING OF DENDRITIC KERATITIS IN THE NEW-ZEALAND RABBIT OCULAR MODEL

Previously, we demonstrated that HPMPC, a new, broad-spectrum antivira l agent, inhibited adenovirus type 5 in the New Zealand (NZ) rabbit oc ular model (Cornea 1992; 11:529-33). Historically, no antiviral agent has been demonstrated to be effective against both herpes simplex viru s type 1 (HSV-1) and adenovirus eye infections in an experimental anim al model. In this study, we compared topical 0.2% HPMPC to 1% trifluri dine and vehicle control in the NZ rabbit HSV-1 keratitis model. Using a double-masked, two-eye design, NZ rabbits were inoculated in both e yes with HSV-1 W strain (10(5) pfu/eye), and dendritic keratitis and H SV-1 ocular titers were measured serially. Compared with the control g roup, both topical 0.2% HPMPC and 1% trifluridine significantly reduce d healing time of HSV-1 dendritic keratitis, lowered HSV-1 ocular tite rs on days 3 through 11, and shortened duration of HSV-1 shedding in t he tear film. For all outcome parameters measured, topical 0.2% HPMPC was as effective as 1% trifluridine. A new concept of a broad-spectrum topical antiviral agent was shown to be effective against HSV-1 in an NZ rabbit keratitis model, and further development toward clinical ap plication appears desirable.