Abstract | 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.
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Authors | Joshua T Schiffer, Amalia Magaret, Stacy Selke, Lawrence Corey, Anna Wald |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 66
Issue 11
Pg. 2593-600
(Nov 2011)
ISSN: 1460-2091 [Electronic] England |
PMID | 21865349
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antiviral Agents
- 2-Aminopurine
- Valine
- Valacyclovir
- Famciclovir
- Acyclovir
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Topics |
- 2-Aminopurine
(administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
- Acyclovir
(administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
- Adult
- Aged
- Antiviral Agents
(administration & dosage, pharmacology, therapeutic use)
- Famciclovir
- Female
- Genitalia
(virology)
- Herpes Genitalis
(drug therapy, transmission, virology)
- Herpesvirus 2, Human
(drug effects, physiology)
- Humans
- Male
- Middle Aged
- Mucous Membrane
(virology)
- Valacyclovir
- Valine
(administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
- Virus Replication
(drug effects)
- Virus Shedding
(drug effects)
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