Inadequacy of plasma acyclovir levels at delivery in patients with genital herpes receiving oral acyclovir suppressive therapy in late pregnancy.
OBJECTIVE
Acyclovir therapy in late pregnancy among women with recurrent genital herpes is effective in decreasing genital lesion frequency and subclinical viral shedding rates at delivery, thereby decreasing the need for Caesarean section. Despite good adherence and increased dosing schedules, breakthrough lesions and viral shedding are still observed in some women at or near delivery. Anecdotal evidence suggests that low levels of herpes simplex virus replication at delivery may result in transmission to the neonate. Therefore, defining optimal acyclovir dosing during labour and delivery is warranted. Our objectives were to determine actual maternal and fetal acyclovir levels at delivery, and explore associations between acyclovir levels, duration of labour, and time since last acyclovir dose.


METHODS
Twenty-seven patients were prescribed oral acyclovir 400 mg three times daily from 36 weeks' gestation. Cord blood (venous and arterial) and maternal venous blood samples were collected at delivery, and acyclovir levels measured using capillary electrophoresis. Correlations between duration of labour, and time since last acyclovir dose with acyclovir blood levels were calculated.


RESULTS
Acyclovir levels were below the published mean steady-state trough value (180 ng/mL) in 52% of venous cord samples, 55% of arterial cord samples, and 36% of maternal samples. There was a significant inverse correlation between the time since last dose and venous cord levels (rs19 = -0.57, P < 0.015), arterial cord levels (rs16 = -0.63, P < 0.01), and maternal acyclovir levels (r10 = -0.69, P < 0.03).


CONCLUSIONS
Oral dosing of acyclovir in women in late pregnancy may result in insufficient levels at delivery to prevent viral shedding. Alternative approaches that incorporate acyclovir dosing through labour, either through oral or intravenous administration, should be evaluated to assess effects on viral shedding.
Leung
Daniel T
DT
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
Henning
Paul A
PA
Wagner
Emily C
EC
Blasig
Audrey
A
Wald
Anna
A
Sacks
Stephen L
SL
Corey
Lawrence
L
Money
Deborah M
DM
D000212:Acyclovir / Q000008:administration & dosage* / Q000097:blood; D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000097:blood; D015331:Cohort Studies; D036861:Delivery, Obstetric; D004305:Dose-Response Relationship, Drug; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D007743:Labor, Obstetric; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D012008:Recurrence; D018139:Simplexvirus; D016896:Treatment Outcome; D017201:Virus Shedding
D000998:Antiviral Agents; D000212:Acyclovir