Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection

Clin Infect Dis. 2014 Feb;58(4):564-72. doi: 10.1093/cid/cit727. Epub 2013 Nov 5.

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.

Keywords: compartmentalization; cytomegalovirus; human immunodeficiency virus; neonates; opportunistic infection.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Lymphocyte Count
  • Cervix Uteri / virology
  • Cytomegalovirus / isolation & purification*
  • Cytomegalovirus Infections / complications*
  • Cytomegalovirus Infections / transmission*
  • Cytomegalovirus Infections / virology
  • Female
  • HIV Infections / complications*
  • HIV Infections / virology
  • HIV-1 / isolation & purification
  • Humans
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical*
  • Milk, Human / virology
  • Plasma / virology
  • Pregnancy
  • Pregnancy Complications, Infectious / virology*
  • Viral Load