title: Reduced markers of HIV persistence and restricted HIV-specific immune responses after early antiretroviral therapy in children.
abstract: OBJECTIVE
  Understanding the extent to which early antiretroviral therapy (ART) can limit the establishment and persistence of the HIV reservoir is an important step to designing interventions aimed at achieving HIV cure. We measured the markers of HIV persistence and HIV-specific immunity in early treated children.
  
  
  METHODS
  This is a cross-sectional study that enrolled 15 children older than 2 years of age who initiated ART before 6 months of age and had sustained viral suppression. Total and integrated HIV DNA, and 2-LTR circles in CD4 T cells, HIV antibody response by fourth generation HIV enzyme immunoassay, and CD4 and CD8 T-cell responses to gag/env peptides by intracellular cytokine staining of CD4 and CD8 T cells were measured.
  
  
  RESULTS
  The median current age was 6.3 years and age at ART initiation was 17 weeks. The median duration of viral suppression was 6 years, and all had HIV RNA less than 50 copies/ml. The median CD4 T cells was 44%. The median total HIV DNA was 132 copies/10 CD4 T cells (range 11-1804) and integrated HIV DNA was 17 copies/10 CD4 T cells (range 0-516), and no one had detectable 2-LTR circles. Nine of the 15 children (60%) had undetectable or extremely low integrated HIV DNA (<20 copies/10 CD4 T cells). All except one (93%) had undetectable HIV-specific CD4/CD8 cell responses and seven (47%) had nonreactive enzyme immunoassay.
  
  
  CONCLUSIONS
  Early ART resulted in very low levels of markers of HIV persistence and undetectable HIV-specific immune responses in the majority of HIV-infected children who started ART before 6 months of age.
authors.affiliation: aThe HIV Netherlands Australia Thailand Research Collaboration bSEARCH, The Thai Red Cross AIDS Research Center cFaculty of Medicine, Department of Medicine dFaculty of Medicine, Department of Pediatrics, Chulalongkorn University eQueen Sirikit National Institute of Child Health fFaculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand gKirby Institute of Infection and Immunity in Society, The University of New South Wales, Sydney, Australia hVaccine and Gene Therapy Institute of Florida, Port St Lucie, Florida, USA.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Thanyawee
authors.initials: T
authors.lastname: Puthanakit
authors.forename: Piyarat
authors.initials: P
authors.lastname: Suntarattiwong
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.forename: Rémi
authors.initials: R
authors.lastname: Fromentin
authors.forename: Wendy
authors.initials: W
authors.lastname: Bakeman
authors.forename: Jintana
authors.initials: J
authors.lastname: Intasan
authors.forename: Apicha
authors.initials: A
authors.lastname: Mahanontharit
authors.forename: Sunee
authors.initials: S
authors.lastname: Sirivichayakul
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D016207:Cytokines; D004279:DNA, Viral; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus