title: Establishment and Replenishment of the Viral Reservoir in Perinatally HIV-1-infected Children Initiating Very Early Antiretroviral Therapy.
abstract: BACKGROUND
  Combination antiretroviral therapy (cART) generally suppresses the replication of the human immunodeficiency virus type 1 (HIV-1) but does not cure the infection, because proviruses persist in stable latent reservoirs. It has been proposed that low-level proviral reservoirs might predict longer virologic control after discontinuation of treatment. Our objective was to evaluate the impact of very early initiation of cART and temporary treatment interruption on the size of the latent HIV-1 reservoir in vertically infected children.
  
  
  METHODS
  This retrospective study included 23 perinatally HIV-1-infected children who initiated very early treatment within 12 weeks after birth (n = 14), or early treatment between week 12 and 1 year (n = 9). We measured the proviral reservoir (CD4(+) T-cell-associated HIV-1 DNA) in blood samples collected beyond the first year of sustained virologic suppression.
  
  
  RESULTS
  There is a strong positive correlation between the time to initiation of cART and the size of the proviral reservoir. Children who initiated cART within the first 12 weeks of life showed a proviral reservoir 6-fold smaller than children initiating cART beyond this time (P < .01). Rapid virologic control after initiation of cART also limits the size of the viral reservoir. However, patients who underwent transient treatment interruptions showed a dramatic increase in the size of the viral reservoir after discontinuation.
  
  
  CONCLUSIONS
  Initiation of cART during the first 12 weeks of life in perinatally HIV-1-infected children limits the size of the viral reservoir. Treatment interruptions should be undertaken with caution, as they might lead to fast and irreversible replenishment of the viral reservoir.
authors.affiliation: Hospital General Universitario Gregorio Marañón Instituto de Investigación Sanitaria Gregorio Marañón Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) Spanish HIV HGM BioBank.
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez-Bonet
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Puertas
authors.affiliation: Unidad de Enfermedades Infecciosas, Servicio de Pediatría, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues del Llobregat.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fortuny
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona.
authors.forename: Dan
authors.initials: D
authors.lastname: Ouchi
authors.affiliation: Servicio de Pediatría Hospitalaria y E. Infecciosas y Tropicales Pediátricas. Hospital Universitario Infantil LA PAZ- H. Carlos III, Madrid.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Mellado
authors.affiliation: Servicio de Pediatría. Hospital 12 de Octubre, Madrid.
authors.forename: Pablo
authors.initials: P
authors.lastname: Rojo
authors.affiliation: Unidad de Enfermedades Infecciosas, Servicio de Pediatría, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues del Llobregat.
authors.forename: Antoni
authors.initials: A
authors.lastname: Noguera-Julian
authors.affiliation: Hospital General Universitario Gregorio Marañón Instituto de Investigación Sanitaria Gregorio Marañón Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) Spanish HIV HGM BioBank.
authors.forename: Ma Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona Universitat de Vic - Universitat Central de Catalunya (UVic-UCC) Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
mesh_terms: D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000706:statistics & numerical data*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D012189:Retrospective Studies; D019562:Viral Load / Q000187:drug effects
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV-1; early antiretroviral therapy; vertical infection; viral reservoir