title: Highly active antiretroviral therapy corrects hematopoiesis in HIV-1 infected patients: interest for peripheral blood stem cell-based gene therapy.
abstract: OBJECTIVE
  To study, in asymptomatic HIV-1-infected (HIV+) patients, whether peripheral blood hematopoietic progenitor/stem cells (PBPC) mobilized by granulocyte colony stimulating factor (G-CSF), can be used as a source of cells for retroviral gene therapy.
  
  
  METHODS
  PBPC from two groups of HIV+ patients (treated or untreated by highly active antiretroviral therapy) and from seronegative donors were mobilized with G-CSF.
  
  
  METHODS
  PBPC collected by leukapheresis were enriched for CD34 cells, immunophenotypically and functionally characterized, cultured and infected with retroviral vectors. HIV proviral integration was studied on fresh and cultured cells.
  
  
  RESULTS
  G-CSF moderately and transiently increased the viral load in untreated patients only, and induced in both groups of HIV+ patients mobilization of percentages and numbers of CD34 cells comparable to those of seronegative volunteers. The most immature CD34 cell subset, the clonogenic progenitor and long-term culture initiating cells were significantly decreased in leukapheresis products and CD34-enriched fractions from untreated HIV+ patients but not in those from treated HIV+ patients. Cell cycle activation and growth factor responses of CD34 cells from both groups of HIV+ patients were not different from those of the control group. Culture and retroviral infection of CD34 cells from HIV+ patients did not enhance HIV replication, and yielded transduction levels similar to those obtained using CD34 cells from seronegative donors.
  
  
  CONCLUSIONS
  G-CSF-mobilized PBPC can be safely used for HIV retroviral gene therapy in asymptomatic treated patients while highly active antiretroviral therapy would control the G-CSF-induced increase in viral load and correct the defective hematopoiesis observed in untreated patients, without inhibiting the retroviral transduction of PBPC.
authors.affiliation: Biologie et Thérapeutique des Pathologies Immunitaires, UMR CNRS Hospital Pitié Salpetriére, Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Baillou
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.forename: Virginie
authors.initials: V
authors.lastname: Leclercq
authors.forename: Nabih
authors.initials: N
authors.lastname: Azar
authors.forename: Michele
authors.initials: M
authors.lastname: Rosenzwajg
authors.forename: Serge
authors.initials: S
authors.lastname: Herson
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: François M
authors.initials: FM
authors.lastname: Lemoine
mesh_terms: D018952:Antigens, CD34; D023241:Antiretroviral Therapy, Highly Active; D015316:Genetic Therapy / Q000379:methods*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000628:therapy; D015497:HIV-1; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D036102:Peripheral Blood Stem Cell Transplantation; D012190:Retroviridae / Q000235:genetics; D018800:Thy-1 Antigens / Q000235:genetics; D014161:Transduction, Genetic / Q000379:methods; D019562:Viral Load; D016662:Virus Integration
chemical_list: D018952:Antigens, CD34; D018800:Thy-1 Antigens; D016179:Granulocyte Colony-Stimulating Factor