PMID- 21865349
OWN - NLM
STAT- MEDLINE
DCOM- 20120321
LR  - 20211020
IS  - 1460-2091 (Electronic)
IS  - 0305-7453 (Print)
IS  - 0305-7453 (Linking)
VI  - 66
IP  - 11
DP  - 2011 Nov
TI  - Detailed analysis of mucosal herpes simplex virus-2 replication kinetics with and 
      without antiviral therapy.
PG  - 2593-600
LID - 10.1093/jac/dkr346 [doi]
AB  - 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.
FAU - Schiffer, Joshua T
AU  - Schiffer JT
AD  - Department of Medicine, University of Washington, Seattle, WA 98102, USA. 
      jschiffe@fhcrc.org
FAU - Magaret, Amalia
AU  - Magaret A
FAU - Selke, Stacy
AU  - Selke S
FAU - Corey, Lawrence
AU  - Corey L
FAU - Wald, Anna
AU  - Wald A
LA  - eng
GR  - K23 AI087206/AI/NIAID NIH HHS/United States
GR  - K24 AI071113/AI/NIAID NIH HHS/United States
GR  - R37 AI042528/AI/NIAID NIH HHS/United States
GR  - P01 AI030731/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110824
PL  - England
TA  - J Antimicrob Chemother
JT  - The Journal of antimicrobial chemotherapy
JID - 7513617
RN  - 0 (Antiviral Agents)
RN  - 452-06-2 (2-Aminopurine)
RN  - HG18B9YRS7 (Valine)
RN  - MZ1IW7Q79D (Valacyclovir)
RN  - QIC03ANI02 (Famciclovir)
RN  - X4HES1O11F (Acyclovir)
SB  - IM
MH  - 2-Aminopurine/administration & dosage/analogs & 
      derivatives/pharmacology/therapeutic use
MH  - Acyclovir/administration & dosage/analogs & derivatives/pharmacology/therapeutic 
      use
MH  - Adult
MH  - Aged
MH  - Antiviral Agents/administration & dosage/pharmacology/*therapeutic use
MH  - Famciclovir
MH  - Female
MH  - Genitalia/*virology
MH  - Herpes Genitalis/*drug therapy/transmission/virology
MH  - Herpesvirus 2, Human/*drug effects/*physiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mucous Membrane/virology
MH  - Valacyclovir
MH  - Valine/administration & dosage/analogs & derivatives/pharmacology/therapeutic use
MH  - Virus Replication/*drug effects
MH  - Virus Shedding/*drug effects
PMC - PMC3191945
EDAT- 2011/08/26 06:00
MHDA- 2012/03/22 06:00
PMCR- 2012/11/01
CRDT- 2011/08/26 06:00
PHST- 2011/08/26 06:00 [entrez]
PHST- 2011/08/26 06:00 [pubmed]
PHST- 2012/03/22 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - dkr346 [pii]
AID - 10.1093/jac/dkr346 [doi]
PST - ppublish
SO  - J Antimicrob Chemother. 2011 Nov;66(11):2593-600. doi: 10.1093/jac/dkr346. Epub 
      2011 Aug 24.