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

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. 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. 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). 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.