title: Patient monitoring and follow-up in lentiviral clinical trials.
abstract: BACKGROUND
  Lentiviral vectors are being used with increasing frequency in human clinical trials. We were the first to use lentiviral vectors in clinical trials in 2003. Our lentiviral vector encoded a long RNA antisense sequence to the HIV-1 envelope and was used in an ex vivo autologous setting to provide viral load control in HIV-1 positive subjects failing anti-HIV therapy. A total of 65 subjects have been treated in Phase 1 and Phase 2 trials in six institutions.
  
  
  METHODS
  Good manufacturing practices (GMP) lots of the lentiviral vector used in our clinical trials were assayed for the presence of replication competent lentivirus (RCL). RCL assays were conducted at two stages. The first testing was performed on samples collected immediately following bulk harvest of the GMP product lot and consisted of 1 × 10(8) cells used in production. RCL assays were also performed on aliquots of the final fill of the vector by the inoculation of at least 5% of the GMP final fill volume into C8166 cells, passaged for at least ten passages and tested for RCL by p24 enzyme-linked immunosorbent assay and vesicular stomatitis virus-G envelope DNA.
  
  
  RESULTS
  Following 263 infusions of autologous, transduced cells, no adverse events have been detected in these subjects, with some followed for more than 8 years following infusions. More than 4.3 × 10(12) VRX496 proviral copies were administered to these 65 subjects.
  
  
  CONCLUSIONS
  Data from this small population suggest that there is no apparent risk for serious adverse events with the use of lentiviral vectors.
authors: VIRxSYS, Corporation, Gaithersburg, MD, USA. bgmcgarr@aol.com
authors: Gerard J
authors: GJ
authors: McGarrity
authors: Gloria
authors: G
authors: Hoyah
authors: April
authors: A
authors: Winemiller
authors: Kris
authors: K
authors: Andre
authors: David
authors: D
authors: Stein
authors: Gary
authors: G
authors: Blick
authors: Richard N
authors: RN
authors: Greenberg
authors: Clifford
authors: C
authors: Kinder
authors: Andrew
authors: A
authors: Zolopa
authors: Gwen
authors: G
authors: Binder-Scholl
authors: Pablo
authors: P
authors: Tebas
authors: Carl H
authors: CH
authors: June
authors: Laurent M
authors: LM
authors: Humeau
authors: Tessio
authors: T
authors: Rebello
mesh_terms: D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D015316:Genetic Therapy / Q000009:adverse effects* / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000032:analysis; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication
chemical_list: C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins