The effect of daily valacyclovir suppression on herpes simplex virus type 2 viral shedding in HSV-2 seropositive subjects without a history of genital herpes.
BACKGROUND
A substantial number of HSV-2 seropositive individuals lack a history of clinically recognized genital herpes. These individuals can transmit disease during periods of asymptomatic viral shedding. The frequency of asymptomatic shedding and the efficacy of antiviral therapy in reducing shedding has not been assessed in this population.


OBJECTIVE
To compare the effect of valacyclovir 1 g once daily for 60 days versus placebo on asymptomatic viral shedding in immunocompetent, HSV-2 seropositive subjects without a history of symptomatic genital herpes infection.


METHODS
Seventy-three subjects were randomized to receive valacyclovir 1 g daily or placebo for 60 days each in a 2-way crossover design. A daily swab of the genital area was self-collected for HSV-2 detection by polymerase chain reaction.


RESULTS
Fifty-six subjects with at least 1 polymerase chain reaction measurement in both treatment periods comprised the primary efficacy population. Valacyclovir significantly reduced shedding during subclinical days compared to placebo [mean, 1.5% vs. 5.1% of subclinical days (P <0.001), a 71% reduction]. Eighty-four percent of subjects had no shedding while receiving valacyclovir versus 54% of subjects on placebo (P <0.001). Eighty-eight percent of patients receiving valacyclovir had no recognized signs or symptoms versus 77% for placebo (P = 0.033). Valacyclovir was not associated with any safety risk compared with placebo.


CONCLUSIONS
In this study, asymptomatic viral shedding occurred in a substantial number of HSV-2 seropositive subjects without a history of genital herpes. Valacyclovir 1 g daily significantly reduced asymptomatic shedding compared with placebo in this population.
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006558:Herpes Genitalis / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome; D014481:United States; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017201:Virus Shedding / Q000187:drug effects
D000914:Antibodies, Viral; D000998:Antiviral Agents; D004279:DNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir