title: CD4+ T cells spontaneously producing human immunodeficiency virus type I in breast milk from women with or without antiretroviral drugs.
abstract: BACKGROUND
  Transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding may involve both cell-free and cell-associated virus. This latter viral reservoir remains, however, to be fully explored. CD4+ T cell-associated virus production in breast milk was therefore investigated.
  
  
  METHODS
  The ex vivo spontaneous production of HIV-1 antigen and HIV-1 RNA by CD4+ T cells was measured in paired blood and breast milk samples from 15 HIV-1 infected women treated or not with antiretroviral drugs. Spontaneous antigen secreting cells (HIV-1-AgSCs) from breast milk and blood were enumerated by an ELISpot assay, and cell-associated HIV-1 RNA was quantified by real-time PCR in supernatants of CD4+ T cells cultured for 18 hours without addition of polyclonal activators.
  
  
  RESULTS
  Among the CD4+ T cells present in breast milk, memory cells expressing high levels of cell-surface activation markers were predominant. Spontaneous HIV-1-AgSCs were detected and enumerated in the breast milk of all 15 women, with a median number of 13.0 and 9.5 HIV-1- AgSCs/106 CD4+ T cells in aviremic (n = 7) and viremic (n = 8) women, respectively. Cell- associated HIV-1 RNA was detected in cell-free supernatants from 4/7 aviremic and 5/8 viremic individuals at median levels of 190 and 245 copies/ml, respectively.
  
  
  CONCLUSIONS
  Activated CD4+ T cells producing HIV-1 are detected in the breast milk of untreated individuals as well as those receiving highly active antiretroviral therapy. This finding strongly suggests that HIV-1 replication occurs in latently infected CD4+ T cells that, upon spontaneous activation, revert to productively infected cells. These cells might be responsible for a residual breast milk transmission despite maternal highly active antiretroviral therapy.
authors.affiliation: Laboratoire Virologie, Centre Muraz, Bobo-Dioulasso, Burkina-Faso.
authors.forename: Diane
authors.initials: D
authors.lastname: Valea
authors.forename: Edouard
authors.initials: E
authors.lastname: Tuaillon
authors.forename: Yassine
authors.initials: Y
authors.lastname: Al Tabaa
authors.forename: François
authors.initials: F
authors.lastname: Rouet
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Rubbo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Meda
authors.forename: Vincent
authors.initials: V
authors.lastname: Foulongne
authors.forename: Karine
authors.initials: K
authors.lastname: Bollore
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
authors.forename: Philippe
authors.initials: P
authors.lastname: Van de Perre
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vendrell
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008895:Milk, Human / Q000166:cytology* / Q000821:virology*; D011247:Pregnancy; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000096:biosynthesis / Q000276:immunology; D014775:Virus Activation
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D014764:Viral Proteins