title: Influence of age at virologic control on peripheral blood human immunodeficiency virus reservoir size and serostatus in perinatally infected adolescents.
abstract: OBJECTIVE
  Combination antiretroviral therapy initiated within several weeks of human immunodeficiency virus (HIV) infection in adults limits proviral reservoirs that preclude HIV cure. Biomarkers of restricted proviral reservoirs may aid in the monitoring of HIV remission or cure.
  
  
  OBJECTIVE
  To quantify peripheral blood proviral reservoir size in perinatally HIV-infected (PHIV+) adolescents and to identify correlates of limited proviral reservoirs.
  
  
  METHODS
  A cross-sectional study including 144 PHIV+ youths (median age, 14.3 years) enrolled in the United States-based Pediatric HIV/AIDS Cohort Study and receiving durable (median duration, 10.2 years) combination antiretroviral therapy, stratified by age at virologic control.
  
  
  METHODS
  The primary end point was peripheral blood mononuclear cell (PBMC) proviral load after virologic control at different ages. Correlations between proviral load and markers of active HIV production (ie, HIV-specific antibodies, 2-long terminal repeat circles) and markers of immune activation and inflammation were also assessed.
  
  
  RESULTS
  Proviral reservoir size was markedly reduced in the PHIV+ youth who achieved virologic control before 1 year of age (4.2 [interquartile range, 2.6-8.6] copies per 1 million PBMCs) compared with those who achieved virologic control at 1 to 5 years of age (19.4 [interquartile range, 5.5-99.8] copies per 1 million PBMCs) or after 5 years of age (70.7 [interquartile range, 23.2-209.4] copies per 1 million PBMCs; P < .001). A proviral burden of less than 10 copies per 1 million PBMCs in PHIV+ youth was measured in 11 (79%), 20 (40%), and 13 (18%) participants with virologic control before 1 year, at 1 to 5 years, and after 5 years of age, respectively (P < .001). Lower proviral load was associated with undetectable 2-long terminal repeat circles (P < .001) and HIV-negative or indeterminate serostatus (P < .001) but not with concentrations of soluble immune activation markers CD14 and CD163.
  
  
  CONCLUSIONS
  Early effective combination antiretroviral therapy with prolonged virologic suppression after perinatal HIV infection leads to negligible peripheral blood proviral reservoirs in adolescence and is associated with negative or indeterminate HIV serostatus. These findings highlight the long-term effect of early effective control of HIV replication on biomarkers of HIV persistence in perinatal infection and the utility of HIV serostatus as a biomarker for small proviral reservoir size, although not necessarily for cure.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Deborah
authors.initials: D
authors.lastname: Persaud
authors.affiliation: Department of Epidemiology and the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Kunjal
authors.initials: K
authors.lastname: Patel
authors.affiliation: Department of Epidemiology and the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Brad
authors.initials: B
authors.lastname: Karalius
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Rainwater-Lovett
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Carrie
authors.initials: C
authors.lastname: Ziemniak
authors.affiliation: Frontier Science and Technology Research Foundation, Inc, Buffalo, New York.
authors.forename: Angela
authors.initials: A
authors.lastname: Ellis
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ya Hui
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla5Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Douglas
authors.initials: D
authors.lastname: Richman
authors.affiliation: Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
authors.forename: George K
authors.initials: GK
authors.lastname: Siberry
authors.affiliation: Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Russell B
authors.initials: RB
authors.lastname: Van Dyke
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Sandra
authors.initials: S
authors.lastname: Burchett
authors.affiliation: Department of Epidemiology and the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: George R
authors.initials: GR
authors.lastname: Seage
authors.affiliation: Program in Molecular Medicine, Department of Pediatrics, University of Massachusetts Medical School, Worcester10Center for Clinical and Translational Science, University of Massachusetts Medical School, Worcester.
authors.forename: Katherine
authors.initials: K
authors.lastname: Luzuriaga
mesh_terms: D000293:Adolescent; D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D011533:Proviruses; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents