title: Cytomegalovirus, and possibly Epstein-Barr virus, shedding in breast milk is associated with HIV-1 transmission by breastfeeding.
abstract: OBJECTIVE
  Postnatal HIV-1 mother-to-child transmission (MTCT) occurs in spite of antiretroviral therapy. Co-infections in breast milk with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are associated with increased HIV-1 shedding in this compartment. We investigated CMV levels and EBV detection in breast milk as potential risk factors for MTCT of HIV-1 via breastfeeding.
  
  
  METHODS
  Cell-free HIV-1 RNA, cell-associated HIV-1 DNA, CMV and EBV DNA were quantified in breast milk from 62 HIV-infected mothers and proven postnatal MTCT of HIV-1 via breastfeeding. Controls were 62 HIV-positive mothers with HIV-uninfected infants.
  
  
  RESULTS
  Median (interquartile range) CMV DNA viral load was significantly higher in cases [88,044 (18,586-233,904)] than in controls [11,167 (3221-31,152)] copies/10 breast milk cells (P < 0.001). Breast milk CMV DNA level correlated positively with breast milk HIV-1 RNA level in cases and controls. EBV DNA was detectable in a higher proportion of breast milk samples of cases (37.1%) than controls (16.1%; P = 0.009). HIV-1 MTCT was strongly associated with HIV-1 RNA shedding in breast milk and plasma. In multivariable analysis, every 1 log10 increase in breast milk CMV DNA was associated with a significant 2.5-fold greater odds of MTCT of HIV-1, independent of breast milk and plasma HIV-1 levels; the nearly three-fold increased risk of HIV-1 MTCT with breast milk EBV DNA detection did not reach significance.
  
  
  CONCLUSIONS
  We provide the first evidence of an independent association between CMV in breast milk, and postnatal MTCT of HIV-1. This association could fuel persistent shedding of HIV-1 in breast milk in women receiving antiretroviral therapy. EBV DNA detection in breast milk may also be associated with MTCT of HIV-1, but only marginally so.
authors.affiliation: aAfrica Centre for Health and Population Studies, University of KwaZulu-Natal, Durban, South Africa bInserm U1058, Université Montpellier 1 cCHRU de Montpellier, Département de Bactériologie-Virologie & Institut de Recherche en Biothérapie and Department of Medical Information, Montpellier, France dRoyal Hospital for Sick Children, Glasgow, UK eDepartment of Paediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa fDepartment of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland gFaculty of Medicine, University of Southampton, Southampton, UK. *Marie-Louise Newell and Philippe van de Perre contributed equally to the writing of this article.
authors.forename: Johannes
authors.initials: J
authors.lastname: Viljoen
authors.forename: Edouard
authors.initials: E
authors.lastname: Tuaillon
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
authors.forename: Siva
authors.initials: S
authors.lastname: Danaviah
authors.forename: Marianne
authors.initials: M
authors.lastname: Peries
authors.forename: Prevashinee
authors.initials: P
authors.lastname: Padayachee
authors.forename: Vincent
authors.initials: V
authors.lastname: Foulongne
authors.forename: Ruth
authors.initials: R
authors.lastname: Bland
authors.forename: Nigel
authors.initials: N
authors.lastname: Rollins
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Newell
authors.forename: Philippe
authors.initials: P
authors.lastname: van de Perre
mesh_terms: D000328:Adult; D001942:Breast Feeding; D016022:Case-Control Studies; D060085:Coinfection; D003587:Cytomegalovirus / Q000502:physiology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008895:Milk, Human / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral