Continuous five‐year treatment of patients with frequently recurring genital herpes simplex virus infection with acyclovir

This study presents data relative to the efficacy and safety following the continuous use of oral acyclovir in the treatment of genital herpes over a 5-year period. In this study, 1,146 patients (53% males; 47% females) were originally enrolled. These included patients with a history of frequently recurring genital herpes (mean >12 episodes per year). During the first year, patients were randomized between those receiving 400 mg of acyclovir twice daily and an equal number receiving placebo. Additionally, acyclovir was utilized for episodic treatment (ES) in both groups. Thereafter, patients received open-label acyclovir suppressive therapy for the remainder of the study period. Complete data are available on 389 patients who completed the fifth year of therapy. All the participants who completed the fifth year of the study had completed either 4 or 5 years of daily suppressive acyclovir therapy. During the first year, a significant decrease in the frequency of recurrences in patients receiving continuous acyclovir (SS) was noted as compared to the placebo group (1.7 vs. 12.5 recurrences; P < 0.0001). From year one to the end of year three, a progressive decrease in the frequency of recurrences was noted in both groups. Yet, those patients who had received SS for the full 3 years had significantly fewer recurrences than those who had received ES in the first year (P = 0.05). During years four and five, the decrease in frequency of recurrences between the ES and SS groups was not significant. During year five of the study, there was a mean annual recurrence rate of 0.8 per patient per year and 66.6% of the patients were completely free of recurrences. Adverse occurrences developed infrequently over the 5 years with a gradual decrease over time. Blood and urine samples were obtained quarterly from each patient for clinical laboratory analysis, including white blood cell count, creatinine, serum, bilirubin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and serum alkaline phosphatase. No significant changes in the mean or median laboratory values were noted. Acyclovir has proven to be effective in the suppression of frequently recurring genital herpes simplex virus infection. Therapy over 5 years has been well tolerated and not associated with serious side effects or cumulative toxicity.