Acyclovir Reduces Recurrence Rate for HSV infection Ophthalmology Times September, 1998 TAMPA After ocular herpes simplex virus (HSV) infection resolves, treatment with acyclovir for 12 months has been shown to reduce the rate of recurrence of ocular and orofacial disease. When acyclovir was administered at a dose of 400 mg twice daily, the rate of recurrence of ocular HSV disease, which is the most common infectious cause of corneal blindness worldwide, dropped by 45%. The authors reported their findings in the July 30 issue of the New England Journal of Medicine. 'Although treatments have been available for active ocular herpes infections to promote resolution, this is the first time a treatment has been conclusively demonstrated to be effective in the prevention of recurrences,' Roy W. Beck, MD, PhD, said. 'In addition to the clinical importance, the findings provide strong circumstantial evidence that stromal keratitis, which had been thought to be produced by an activated immune response without active virus, may be initiated by viral replication,' he continued. Dr. Beck was the director of the National Coordinating Center of the Herpetic Eye Disease Study Group and is director of the Jaeb Center for Health Research, Tampa. The study, funded by the National Eye Institute, was a randomized, placebo-controlled trial of 18 months duration that was conducted at 74 clinical sites in the U.S.; 703 patients were enrolled, with 357 receiving acyclovir and 346 receiving placebo. Patients were eligible for participation in the study if they had had ocular HSV disease (blepharitis, conjunctivitis, epithelial or stromal keratitis, or iritis) within the previous 12 months and if the disease was inactive for 30 days before enrollment. Patients were excluded if they were receiving antiviral or immunosuppressive therapy, if they had a history of immune dysfunction or renal insufficiency, if acyclovir therapy was contraindicated, or if they had undergone keratoplasty or keratorefractive surgery of the affected eye. The patients were randomly assigned to receive active treatment (400 mg of oral acyclovir administered twice a day in two capsules for 12 months) or placebo. Patients were examined at 1, 3, 6, 9, and 12 months after the start of treatment and then after months 13, 15, and 18. A total of 575 patients (82%) completed the 12 months of treatment. No serious adverse effects occurred during treatment, according to the authors. 'The cumulative probability of a recurrence of ocular HSV disease during the 12-month treatment period was significantly lower in the acyclovir group than in the placebo group (19% versus 32%; rate ratio, 0.55; 95% confidence interval, 0.41 to 0.75;p < 0.001). Past episodes significant The data also showed that the number of previous episodes of HSV disease affected the recurrence rate. 'In both treatment groups, the number of past episodes of ocular HSV disease was strongly associated with the likelihood of a recurrence (p = 0.04 in the acyclovir group and p = 0.006 in the placebo group),' the authors said. The cumulative probability of a recurrence during the treatment period was determined using the Kaplan-Meier produce limit method. For example, of the 101 patients in the acyclovir group who had had one previous episode of HSV disease, the cumulative probability of recurrence was 13%. In the 141 patients receiving acyclovir who had had four or more previous episodes of HSV disease, the probably of a recurrence was 25%. When the authors analyzed the efficacy data based on the type of HSV disease, they found that in the 337 patients who had a history of stromal keratitis, the probability of a recurrence was 14% in the group of patients who received acyclovir and 28% in the placebo group (p = 0.005). The results were similar for epithelial keratitis. The recurrence rate of orofacial HSV disease was also significantly lower in the acyclovir group compared with the placebo group (19% versus 36%, respectively; p < 0.001). In those patients who had a history of orofacial HSV disease, the cumulative probability of an orofacial recurrence during the 12-month treatment period was 29% in 170 patients in the acyclovir group and 50% in 177 patients in the placebo group, the authors reported. 'Our results show that long-term treatment with acyclovir helps prevent recurrences of ocular HSV disease and orofacial HSV infections in patients with a history of ocular HSV disease. 'Since the form that a recurrence of ocular HSV disease takes is strongly associated with the form of previous episodes, prolonged acyclovir therapy should provide the greatest clinical benefit for patients with a history of stromal keratitis because it should reduce the likelihood of the corneal scarring and loss of vision that can result from recurrent episodes of stromal keratitis,' the authors concluded. They noted that the role of acyclovir as prophylactic therapy is not certain in patients who have had superficial forms of ocular HSV disease, such as epithelial keratitis, conjunctivitis, and blepharitis. These manifestations of the disease respond to short-term topical antiviral therapy and generally do not result in permanent damage.