Antiviral Treatment for Genital Herpes

A sudy 2 analyzed prospective data from natural history studies and clinical trials of antiviral agents for HSV-2 in which HSV-2-seropositive participants (n=674) provided self-collected anogenital swab specimens daily over ≥25 days. Genital HSV shedding was detected on 17% of days, and genital lesions were reported on 10% of days. HSV shedding rates were strongly correlated with lesion rates (ρ = 0.61, P < .0001). The relative reduction in the recurrence rate was 72% (P = .041) with antiviral agent pritelivir as compared to placebo, but it decreased to 21% (P = .75) after adjustment for HSV shedding rate. When evaluating valacyclovir and acyclovir, adjustment for the HSV shedding rate also led to a reduced association of these antivirals with the recurrence rate. Overall, 40% to 82% of the antiviral effect on recurrences was explained by its effect on HSV shedding.

A meta-analysis 3 included 14 RCTs with a total of 6158 patients. The global relative risk of developing at least one recurrence during the study was reduced by 47% (95% CI 45% to 49%) with antiviral drugs compared to placebo. The best evaluated regimens, with comparable efficacies, were given twice daily, ie, acyclovir (400 mg twice daily), valacyclovir (250 mg twice daily), and famciclovir (250 mg twice daily), or once daily valacyclovir (500 mg).

A topic in Clinical Evidence 1 summarizes the results of one non-systematic review (5 RCTs, 650 people) and one subsequent RCT. The review found that aciclovir reduced the duration of viral shedding and duration of lesions compared with placebo (5 days with aciclovir vs 6 days with placebo). The subsequent RCT (n=131) found that aciclovir 800 mg 3 times daily for 2 days reduced the duration of lesions, episodes, and viral shedding compared with placebo (duration of lesions 4 days vs 6 days, duration of episodes 4 days vs 6 days, duration of viral shedding 25 hours vs 58.5 hours). Oral famciclovir (1 RCT), and oral valaciclovir (1 RCT) significantly reduced the duration of lesions and viral shedding. There was no difference between valaciclovir vs aciclovir (1 RCT) and between 3 days and 5 days of valaciclovir (2 RCTs).

References

• Jungmann E. What are the effects of interventions to reduce the impact of recurrence? Genital herpes. Clinical Evidence 2005;13:1990-2001.
• Agyemang E, Magaret AS, Selke S et al. Herpes Simplex Virus Shedding Rate: Surrogate Outcome for Genital Herpes Recurrence Frequency and Lesion Rates, and Phase 2 Clinical Trials End Point for Evaluating Efficacy of Antivirals. J Infect Dis 2018;218(11):1691-1699. [PubMed]
• Lebrun-Vignes B, Bouzamondo A, Dupuy A et al. A meta-analysis to assess the efficacy of oral antiviral treatment to prevent genital herpes outbreaks. J Am Acad Dermatol 2007;57(2):238-46. [PubMed]