Acyclovir sensitivity of sequential herpes simplex virus type 2 isolates from the genital mucosa of immunocompetent women.
BACKGROUND
Despite widespread use of acyclovir, infection with acyclovir-resistant herpes simplex virus type 2 (HSV-2) remains uncommon. To understand the frequency and clinical significance of acyclovir-resistant isolates, we evaluated the in vitro acyclovir sensitivities of sequential isolates from 34 immunocompetent women.


METHODS
HSV-2-seropositive women collected daily samples of genital secretions while receiving acyclovir or placebo, each for 10 weeks. In vitro acyclovir sensitivity testing was performed using the dye uptake assay; isolates for which the concentration of acyclovir that inhibited cytopathic effect by 50% (EC50) was > or = 3 microg/mL were defined as resistant.


RESULTS
A total of 351 isolates from 26 women were tested (median, 10 isolates/woman [range, 3-45 isolates/woman]). The median EC50 was 0.91 microg/mL. Overall, 7 isolates (1.7%) from 6 women had EC50 values > or = 3 microg/mL. None of the women was receiving acyclovir when the acyclovir-resistant isolates were detected. Acyclovir-sensitive and acyclovir-resistant isolates were detected in samples collected on the same day from separate anatomic sites in 3 women. The acyclovir-resistant isolates were transient, because acyclovir-sensitive isolates were obtained before and after the acyclovir-resistant isolates from 5 women were detected.


CONCLUSIONS
Among immunocompetent women, the finding of acyclovir-resistant HSV-2 isolates likely represents transient mucosal variants and does not predict treatment failure.
Gupta
Rachna
R
Department of Medicine, University of Washington, Seattle, USA. rachnabanner@aol.com
Hill
Edgar L
EL
McClernon
Dan
D
Davis
Gray
G
Selke
Stacy
S
Corey
Lawrence
L
Wald
Anna
A
D000212:Acyclovir / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D001826:Body Fluids / Q000821:virology; D005260:Female; D005836:Genitalia, Female / Q000821:virology*; D006558:Herpes Genitalis / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000302:isolation & purification*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009092:Mucous Membrane / Q000821:virology*
D000998:Antiviral Agents; D000212:Acyclovir