Detailed analysis of mucosal herpes simplex virus-2 replication kinetics with and without antiviral therapy.

OBJECTIVES: The presence of herpes simplex virus-2 (HSV-2) shedding episodes correlates with transmission to sexual partners and neonates, and some episodes correlate with disease manifestations. HSV-2-targeted guanosine analogues are effective when given on a prophylactic basis, but do not completely eliminate recurrences, asymptomatic shedding or transmission. We sought to describe the impact of twice-daily aciclovir and famciclovir on shedding episodes.
METHODS: We used pooled results from crossover clinical trials to construct frequency histograms for viral shedding episode duration, peak copy number, expansion kinetics and decay kinetics.
RESULTS: Suppressive aciclovir and famciclovir decreased the frequency of episodes of >24 h duration by 50%, lowered the mean early episode expansion rate (from 8.2 to 7.2 HSV DNA logs/day, P = 0.004), decreased the mean peak values for shedding episodes (from 4.9 to 3.9 log(10) HSV DNA copies/mL, P < 0.001) and lowered the mean episode duration (from 4.8 to 2.1 days, P < 0.001) primarily by decreasing the probability of viral re-expansion during episodes. The mean rate of late viral decay was similar for persons on and off antiviral medications (-6.0 versus -5.8 HSV DNA logs/day, P = 0.61).
CONCLUSIONS: HSV-2-targeted antiviral therapy limits episode severity by decreasing the rate of early viral expansion and the likelihood of episode re-expansion. Late clearance of episodes in the immunocompetent host is not affected by antiviral therapy, suggesting that local immune response is critical for clearance of episodes both on and off treatment.