title: Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding.
abstract: BACKGROUND
  Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.
  
  
  METHODS
  Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.
  
  
  RESULTS
  There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33-4.59) vs. aHR 1.52 (95% CI, 1.17-1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64-3.92) vs. 1.73 (95% CI 0.94-3.19), respectively].
  
  
  CONCLUSIONS
  The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.
authors.affiliation: Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa. jndirangu@africacentre.ac.za
authors.forename: James
authors.initials: J
authors.lastname: Ndirangu
authors.forename: Johannes
authors.initials: J
authors.lastname: Viljoen
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Bland
authors.forename: Siva
authors.initials: S
authors.lastname: Danaviah
authors.forename: Claire
authors.initials: C
authors.lastname: Thorne
authors.forename: Philippe
authors.initials: P
authors.lastname: Van de Perre
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Newell
mesh_terms: D000328:Adult; D001942:Breast Feeding / Q000009:adverse effects*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000706:statistics & numerical data*; D008895:Milk, Human / Q000821:virology*; D049590:Postpartum Period; D012367:RNA, Viral / Q000032:analysis*; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral