title: CCR5 Δ32 homozygous cord blood allogeneic transplantation in a patient with HIV: a case report.
abstract: BACKGROUND
  Allogeneic donor CCR5 Δ32 homozygous haemopoietic cell transplantation (HCT) provides the only evidence to date of long-term control of HIV infection. However, availability of conventional CCR5 Δ32 homozygous donors is insufficient to develop this as a therapeutic strategy further.
  
  
  METHODS
  We present a 37-year-old patient with HIV-1 infection and aggressive lymphoma who had disease progression after five lines of radiochemotherapy including an autologous HCT, and in the absence of matched sibling donors, received an allogeneic HCT with four of six HLA-matched CCR5 Δ32 homozygous cord blood cells (StemCyte, Covina, CA), supported with purified CD34+ cells from a haploidentical sibling. Blood or tissue samples were obtained before and weekly after HCT to monitor transplant and HIV infection, including chimerism analysis, CCR5 genotyping and viral tropism, viral isolation and sequence, viral reservoir analysis, immune activation and proliferation, and ex-vivo cell infectivity assays. Combined antiretroviral therapy continued during the procedure.
  
  
  RESULTS
  The patient's HIV was CCR5-tropic by genotypic and phenotypic analyses. Baseline latent reservoir tests showed HIV DNA copies in bulk and resting CD4 T cells and in gut-associated lymphoid tissue, CD4 T-cell-associated HIV RNA, replication competent viral size of 2·1 copies per 10(7) CD4 T cells, and single copy assay of 303 copies per mL. After HCT, plasma HIV DNA load was undetectable by ultrasensitive analyses. Upon cord blood full chimerism, the patient's CCR5 Δ32 homozygous CD4 T cells responded to proliferation and activation stimuli and became resistant to infection by the patient's viral isolate and by laboratory-adapted HIV-1 strains. Death related to lymphoma progression regretfully prevented long-term monitoring of the patient's viral reservoir.
  
  
  CONCLUSIONS
  CCR5 Δ32 homozygous cord blood reconstitution can successfully eliminate HIV-1 and render the allogeneic graft recipient's T lymphocytes resistant to HIV infection. Thus, they build on the evidence available to strongly support the use of cord blood as a strategic platform for a broader application of non-functional CCR5 transplantation to other infected individuals.
  
  
  BACKGROUND
  Spanish Secretariat of Research, the American Foundation for AIDS Research (amfAR).
authors.affiliation: Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: rafaduarte@me.com.
authors.forename: Rafael F
authors.initials: RF
authors.lastname: Duarte
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Cièncias de la Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Salgado
authors.affiliation: Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sánchez-Ortega
authors.affiliation: Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Arnan
authors.affiliation: Banc de Sang i Teixits and Cord Blood Bank, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Canals
authors.affiliation: Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Domingo-Domenech
authors.affiliation: Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-de-Sevilla
authors.affiliation: Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Cièncias de la Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Morón-López
authors.affiliation: Banc de Sang i Teixits and Cord Blood Bank, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Nogues
authors.affiliation: Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Patiño
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Cièncias de la Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Puertas
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Cièncias de la Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain; Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Barcelona, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.affiliation: StemCyte International Cord Blood Center; Covina, CA, USA.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Petz
authors.affiliation: Banc de Sang i Teixits and Cord Blood Bank, Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Querol
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Cièncias de la Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain; Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Barcelona, Spain; Catalan Institution for Research and Advanced Studies; Barcelona, Spain. Electronic address: jmpicado@irsicaixa.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
mesh_terms: D000328:Adult; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000637:transplantation*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006720:Homozygote; D006801:Humans; D008297:Male; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: C584933:CCR5 protein, human; D019713:Receptors, CCR5