title: Infant safety during and after maternal valacyclovir therapy in conjunction with antiretroviral HIV-1 prophylaxis in a randomized clinical trial.
abstract: BACKGROUND
  Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described.
  
  
  METHODS
  Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm(3) were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher's Exact and Wilcoxon rank-sum tests were used for analysis.
  
  
  RESULTS
  One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6-4.19).
  
  
  CONCLUSIONS
  Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00530777.
authors.affiliation: Department of Global Health, University of Washington, Seattle, Washington, United States of America. adrake2@uw.edu
authors.forename: Alison L
authors.initials: AL
authors.lastname: Drake
authors.forename: Alison C
authors.initials: AC
authors.lastname: Roxby
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
mesh_terms: D000212:Acyclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D060085:Coinfection / Q000635:transmission; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008895:Milk, Human / Q000737:chemistry; D009035:Mothers; D049590:Postpartum Period / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D013997:Time Factors; D000077483:Valacyclovir; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir