title: Relationship between CCR5(WT/Δ32)heterozygosity and HIV-1 reservoir size in adolescents and young adults with perinatally acquired HIV-1 infection.
abstract: BACKGROUND
  Several host factors contribute to human immunodeficiency virus (HIV) disease progression in the absence of combination antiretroviral therapy (cART). Among them, the CC-chemokine receptor 5 (CCR5) is known to be the main co-receptor used by HIV-1 to enter target cells during the early stages of an HIV-1 infection.
  
  
  OBJECTIVE
  We evaluated the association of CCR5(WT/Δ32)heterozygosity with HIV-1 reservoir size, lymphocyte differentiation, activation and immunosenescence in adolescents and young adults with perinatally acquired HIV infection receiving cART.
  
  
  METHODS
  CCR5 genotype was analysed in 242 patients with vertically transmitted HIV-1 infection from Paediatric Spanish AIDS Research Network Cohort (coRISpe). Proviral HIV-1 DNA was quantified by digital-droplet PCR, and T-cell phenotype was evaluated by flow cytometry in a subset of 24 patients (ten with CCR5(Δ32/WT)genotype and 14 with CCR5(WT/WT)genotype).
  
  
  RESULTS
  Twenty-three patients were heterozygous for the Δ32 genotype but none was homozygous for the mutated CCR5 allele. We observed no difference in the HIV-1 reservoir size (455 and 578 copies of HIV-1 DNA per million CD4+T cells in individuals with CCR5(WT/WT)and CCR5(Δ32/WT)genotypes, respectively; p 0.75) or in the immune activation markers between both genotype groups. However, we found that total HIV-1 DNA in CD4+T cells correlated with the percentage of memory CD4+T cells: a direct correlation in CCR5(WT/Δ32)patients but an inverse correlation in those with the CCR5(WT/WT)genotype.
  
  
  CONCLUSIONS
  This finding suggests a differential distribution of the viral reservoir compartment in CCR5(WT/Δ32)patients with perinatal HIV infection, which is a characteristic that may affect the design of strategies for reservoir elimination.
authors.affiliation: Laboratory of Immuno Molecular Biology, Section of Immunology, Hospital General Universitario Gregorio Marañon, IiSGM, Madrid, Spain; Spanish HIV HGM BioBank, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martínez-Bonet
authors.affiliation: Laboratory of Immuno Molecular Biology, Section of Immunology, Hospital General Universitario Gregorio Marañon, IiSGM, Madrid, Spain; Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors.forename: A
authors.initials: A
authors.lastname: González-Serna
authors.affiliation: Laboratory of Immuno Molecular Biology, Section of Immunology, Hospital General Universitario Gregorio Marañon, IiSGM, Madrid, Spain; Spanish HIV HGM BioBank, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: M I
authors.initials: MI
authors.lastname: Clemente
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Morón-López
authors.affiliation: Laboratory of Immuno Molecular Biology, Section of Immunology, Hospital General Universitario Gregorio Marañon, IiSGM, Madrid, Spain; Spanish HIV HGM BioBank, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Díaz
authors.affiliation: Department of Infection Disease Section, Paediatric Service, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Navarro
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Puertas
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Leal
authors.affiliation: Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; Universitat de Vic - Universitat Central de Catalunya (UVic-UCC), Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. Electronic address: jmpicado@irsicaixa.es.
authors.forename: J
authors.initials: J
authors.lastname: Martinez-Picado
authors.affiliation: Laboratory of Immuno Molecular Biology, Section of Immunology, Hospital General Universitario Gregorio Marañon, IiSGM, Madrid, Spain; Spanish HIV HGM BioBank, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. Electronic address: mmunoz.hgugm@gmail.com.
authors.forename: M A
authors.initials: MA
authors.lastname: Muñoz-Fernández
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000175:diagnosis*; D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D060005:Genotyping Techniques; D015658:HIV Infections / Q000175:diagnosis*; D015497:HIV-1; D006801:Humans; D008297:Male; D011247:Pregnancy; D019713:Receptors, CCR5 / Q000235:genetics*; D012189:Retrospective Studies; D019562:Viral Load; D055815:Young Adult
chemical_list: C584933:CCR5 protein, human; D004279:DNA, Viral; D019713:Receptors, CCR5
keywords: Adolescents; CCR5((WT/Δ32)); Human immunodeficiency virus-1; Reservoir size; Young adults