Once-Daily Valacyclovir to Reduce the Risk of Transmission of Genital Herpes Corey L et al. N Engl J Med. 2004;350:11
The authors performed a prospective, randomized, placebo-controlled trial of valacyclovir (500 mg/d for 8 months) in 1484 immunocompetent, heterosexual, monogamous couples that were discordant for HSV-2 symptomatic genital infection. A subset analysis was done in 89 patients to determine the effect of valacyclovir on viral shedding using HSV PCR analysis of genital swab specimens. The results were analyzed by the number of symptomatic genital infections in the source patient, the number of newly acquired genital infections in the partner who was negative at baseline, and the percent days of viral shedding. The results are shown in the table below:
The authors conclude that valacyclovir given once daily to a patient with genital herpes significantly reduces the rate of HSV transmission.
Comment: The potential value of acyclovir or valacyclovir and related agents to prevent clinical episodes of genital herpes is well established. The importance of this study was the demonstration that this suppression, not surprisingly, also prevents transmission to sexual partners. The biologic reason is not rocket science; as demonstrated in the study, viral shedding is notably reduced in the source patient. The potential application of this information is important for couples who are discordant for HSV. However, as noted in the editorial by Clyde Crumpacker (N Engl J Med. 2004;350:67), this may have even more important application for reducing transmission of HIV infection. HSV is the leading cause of genital ulcers in both developed and developing countries. These ulcers have high concentrations of HIV in coinfected patients (JAMA. 1998;280:61). In terms of the practical application of these data, the obvious concern might be the expense, safety, and concern for resistance. A recent report of HSV isolates from genital lesions in 2088 patients attending STD clinics showed that only 0.2% were resistant to acyclovir (Arch Intern Med. 2003;163:76). The safety profile of these drugs is well established by the extensive use of acyclovir which has been used in millions, since it was introduced in 1982. In terms of cost, Dr Crumpacker notes that generic acyclovir at 400 mg twice daily costs about US$73/year.