Famciclovir Reduces Viral Mucosal Shedding in HSV-Seropositive Persons

Abstract

Many cases of herpes simplex virus (HSV) infection occur through asymptomatic shedding from persons without evidence of clinical disease. This study explores whether famciclovir reduces HSV shedding in HSV-2 seropositive persons with or without a history of symptomatic genital herpes. One hundred twenty-seven HSV-2 seropositive participants were randomly assigned to 42 days of famciclovir, followed by 14 days of washout and 42 days of placebo, or vice versa. All subjects swabbed the genital/perianal area; those with HSV-1 infection also swabbed the oral area daily for HSV DNA PCR. Famciclovir reduced genital and oral HSV shedding from 11.4% of days during the placebo period to 4.7% of days during famciclovir therapy. The reduction was greater in participants with a history of genital herpes (74%) than in those without such a history (30%). In multivariate analyses, famciclovir protected against total (clinical and subclinical) genital shedding among persons with a clinical history of genital herpes (RR, 0.23; 95% CI, 0.15-0.35; P < 0.001). Among HSV-2 seropositive participants without a history of genital herpes, 60% had HSV detected in the genital area at least once during the study. Famciclovir therapy did not result in a statistically significant reduction in total HSV shedding in participants without a history of genital herpes. Famciclovir therapy decreases genital HSV shedding in HSV-seropositive persons, especially those with a history of genital herpes. Overall, antiviral drugs may have varying effects on symptomatic and asymptomatic viral shedding, depending on the clinical history of the disease.