title: Early initiation of combination antiretroviral therapy in HIV-1-infected newborns can achieve sustained virologic suppression with low frequency of CD4+ T cells carrying HIV in peripheral blood.
abstract: BACKGROUND
  A human immunodeficiency virus type 1 (HIV-1)-infected infant started on combination antiretroviral therapy (cART) at 30 hours of life was recently reported to have no detectable plasma viremia after discontinuing cART. The current study investigated the impact of early cART initiation on measures of HIV-1 reservoir size in HIV-1-infected children with sustained virologic suppression.
  
  
  METHODS
  Children born to HIV-1-infected mothers and started on cART within 72 hours of birth at 3 Canadian centers were assessed. HIV serology, HIV-1-specific cell-mediated immune responses, plasma viremia, cell-associated HIV-1 DNA and RNA, presence of replication-competent HIV-1, and HLA genotype were determined for HIV-1-infected children with sustained virologic suppression.
  
  
  RESULTS
  Of 136 cART-treated children, 12 were vertically infected (8.8%). In the 4 who achieved sustained virologic suppression, HIV serology, HIV-1-specific cell-mediated immune responses (Gag, Nef), and ultrasensitive viral load were negative. HIV-1 DNA was not detected in enriched CD4(+) T cells of the 4 children (<2.6 copies/10(6) CD4(+) T cells), whereas HIV-1 RNA was detected (19.5-130 copies/1.5 µg RNA). No virion-associated HIV-1 RNA was detected following mitogenic stimulation of peripheral blood CD4(+) T cells (5.4-8.0 million CD4(+) T cells) in these 4 children, but replication competent virus was detected by quantitative co-culture involving a higher number of cells in 1 of 2 children tested (0.1 infectious units/10(6) CD4(+) T cells).
  
  
  CONCLUSIONS
  In perinatally HIV-1-infected newborns, initiation of cART within 72 hours of birth may significantly reduce the size of the HIV-1 reservoirs. Cessation of cART may be necessary to determine whether functional HIV cure can be achieved in such children.
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, University of Toronto.
authors.forename: Ari
authors.initials: A
authors.lastname: Bitnun
authors.affiliation: Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ontario, Canada.
authors.forename: Lindy
authors.initials: L
authors.lastname: Samson
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chun
authors.affiliation: Department of Pediatrics, CHU Sainte-Justine.
authors.forename: Fatima
authors.initials: F
authors.lastname: Kakkar
authors.affiliation: Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ontario, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Brophy
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Danielle
authors.initials: D
authors.lastname: Murray
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Shawn
authors.initials: S
authors.lastname: Justement
authors.affiliation: Centre de recherche du CHU Sainte-Justine, Department of Microbiology, Infectiology and Immunology, and Department of Pediatrics, Université de Montréal, Quebec.
authors.forename: Hugo
authors.initials: H
authors.lastname: Soudeyns
authors.affiliation: Department of Immunology and Medicine, University of Toronto, and Keenan Centre for Biomedical Research of St Michael's Hospital, Toronto.
authors.forename: Mario
authors.initials: M
authors.lastname: Ostrowski
authors.affiliation: Institute of Medical Sciences, Department of Medicine, University of Toronto, Ontario.
authors.forename: Shariq
authors.initials: S
authors.lastname: Mujib
authors.affiliation: Department of Medicine, BC Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver.
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.affiliation: National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.affiliation: National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Sandstrom
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, University of Toronto.
authors.forename: Stanley E
authors.initials: SE
authors.lastname: Read
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002170:Canada; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
keywords: HIV; child; combination antiretroviral therapy; eradication; proviral DNA