title: Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection.
abstract: BACKGROUND
  Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)-exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined.
  
  
  METHODS
  CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1-infected women to define correlates of maternal CMV replication and infant CMV acquisition.
  
  
  RESULTS
  Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (β = 0.47; P = .005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P = .003) and maternal CD4 < 450 cells/mm(3) (HR, 1.8; P = .008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm(3) to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm(3).
  
  
  CONCLUSIONS
  Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.
authors.affiliation: Departments of Global Health.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Slyker
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
authors.forename: Claire
authors.initials: C
authors.lastname: Atkinson
authors.forename: Kristjana
authors.initials: K
authors.lastname: Ásbjörnsdóttir
authors.forename: Alison
authors.initials: A
authors.lastname: Roxby
authors.forename: Alison
authors.initials: A
authors.lastname: Drake
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.forename: Barbra
authors.initials: B
authors.lastname: Richardson
authors.forename: Katherine
authors.initials: K
authors.lastname: Odem-Davis
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
authors.forename: Vincent
authors.initials: V
authors.lastname: Emery
mesh_terms: D018791:CD4 Lymphocyte Count; D002584:Cervix Uteri / Q000821:virology; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000635:transmission* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008895:Milk, Human / Q000821:virology; D010949:Plasma / Q000821:virology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D019562:Viral Load
keywords: compartmentalization; cytomegalovirus; human immunodeficiency virus; neonates; opportunistic infection