title: Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women.
abstract: BACKGROUND
  Studies in HIV-1-infected infants and HIV-1-exposed, uninfected infants link early cytomegalovirus (CMV) acquisition with growth delay and cognitive impairment. We investigated maternal valacyclovir to delay infant acquisition of CMV.
  
  
  METHODS
  Pregnant women with HIV-1, HSV-2 and CD4 count >250 cells/µl were randomized at 34 weeks gestation to 500 mg twice-daily valacyclovir or placebo for 12 months. Maternal CMV DNA was measured in plasma at 34 weeks gestation, in cervical secretions at 34 and 38 weeks gestation, and in breast milk at 7 postpartum timepoints; infant CMV DNA was measured in dried blood spots at 8 timepoints including birth.
  
  
  RESULTS
  Among 148 women, 141 infants were compared in intent-to-treat analyses. Maternal and infant characteristics were similar between study arms. Infant CMV acquisition did not differ between study arms, with 46/70 infants (66%) in placebo arm and 47/71 infants (66%) in the valacyclovir arm acquiring CMV; median time to CMV detection did not differ. CMV DNA was detected in 92% of 542 breast milk specimens with no difference in CMV level between study arms. Change in cervical shedding of CMV DNA between baseline and 38 weeks was 0.40-log greater in the placebo arm than the valacyclovir arm (p = 0.05).
  
  
  CONCLUSIONS
  In this cohort of HIV-1-seropositive mothers, two-thirds of infants acquired CMV by one year. Maternal valacyclovir had no effect on timing of infant CMV acquisition or breast milk CMV viral loads, although it modestly reduced cervical CMV shedding. Maternal prophylaxis to reduce infant CMV acquisition warrants further evaluation in trials with antiviral agents.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00530777.
authors: Department of Medicine, University of Washington, Seattle, Washington, United States of America.
authors: Alison C
authors: AC
authors: Roxby
authors: Centre for Virology, Department of Infection, School of Biomedical and Life Sciences, University College London, London, United Kingdom.
authors: Claire
authors: C
authors: Atkinson
authors: Department of Epidemiology, University of Washington, Seattle, Washington, United States of America.
authors: Kristjana
authors: K
authors: Asbjörnsdóttir
authors: Department of Medicine, University of Washington, Seattle, Washington, United States of America ; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America ; Department of Global Health, University of Washington, Seattle, Washington, United States of America.
authors: Carey
authors: C
authors: Farquhar
authors: Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya.
authors: James N
authors: JN
authors: Kiarie
authors: Department of Global Health, University of Washington, Seattle, Washington, United States of America.
authors: Alison L
authors: AL
authors: Drake
authors: Department of Medicine, University of Washington, Seattle, Washington, United States of America ; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America ; Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America ; Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Anna
authors: A
authors: Wald
authors: Department of Medicine, University of Washington, Seattle, Washington, United States of America ; Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America ; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Michael
authors: M
authors: Boeckh
authors: Department of Global Health, University of Washington, Seattle, Washington, United States of America ; Department of Biostatistics, University of Washington, Seattle, Washington, United States of America ; Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors: Barbra
authors: B
authors: Richardson
authors: Department of Microbial and Cellular Science, University of Surrey, Guildford, United Kingdom.
authors: Vincent
authors: V
authors: Emery
authors: Department of Medicine, University of Washington, Seattle, Washington, United States of America ; Department of Epidemiology, University of Washington, Seattle, Washington, United States of America ; Department of Global Health, University of Washington, Seattle, Washington, United States of America ; Department of Pediatrics, University of Washington, Seattle, Washington, United States of America.
authors: Grace
authors: G
authors: John-Stewart
authors: Department of Global Health, University of Washington, Seattle, Washington, United States of America.
authors: Jennifer A
authors: JA
authors: Slyker
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D005260:Female; D006679:HIV Seropositivity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008895:Milk, Human / Q000821:virology; D011247:Pregnancy; D011292:Premedication; D016896:Treatment Outcome; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019562:Viral Load; D017201:Virus Shedding
chemical_list: D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir