title: Preferential survival of CD4+ T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals.
abstract: The present study examined the safety and relative in vivo survival of genetically engineered CD4+ T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. Ten pairs of identical twins discordant for HIV infection were recruited, with the uninfected twin serving as the lymphocyte donor. Ten subjects were treated with a total of 19 separate infusions of retroviral vector-transduced CD4+ enriched T cells. Control (neo gene) or anti-HIV gene (antisense trans-activation response [TAR] element and/or trans-dominant Rev)-engineered lymphocytes were monitored in peripheral blood for 3 years, using a vector-specific PCR assay. Data from 9 of the 10 patients (15 of the 19 infusions) demonstrated preferential survival of CD4+ lymphocytes containing the anti-HIV gene(s) in the immediate weeks after infusion. In six of six patients studied long term (>100 weeks), only T cells containing the anti-HIV genes were consistently detected. In addition, a marked survival advantage of anti-HIV gene-containing T cells was observed in a patient treated during a period of high viral load. Thus, these data strongly support the hypothesis that anti-HIV genes afford a survival advantage to T cells and potential benefit to HIV-1+ individuals.
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morgan
authors.forename: Robert
authors.initials: R
authors.lastname: Walker
authors.forename: Charles S
authors.initials: CS
authors.lastname: Carter
authors.forename: Ven
authors.initials: V
authors.lastname: Natarajan
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Tavel
authors.forename: Chris
authors.initials: C
authors.lastname: Bechtel
authors.forename: Betsy
authors.initials: B
authors.lastname: Herpin
authors.forename: Linda
authors.initials: L
authors.lastname: Muul
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zheng
authors.forename: Shyla
authors.initials: S
authors.lastname: Jagannatha
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bunnell
authors.forename: Vicki
authors.initials: V
authors.lastname: Fellowes
authors.forename: Julia A
authors.initials: JA
authors.lastname: Metcalf
authors.forename: Randy
authors.initials: R
authors.lastname: Stevens
authors.forename: Michael
authors.initials: M
authors.lastname: Baseler
authors.forename: Susan F
authors.initials: SF
authors.lastname: Leitman
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Read
authors.forename: R Michael
authors.initials: RM
authors.lastname: Blaese
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D002470:Cell Survival / Q000235:genetics; D004200:Diseases in Twins; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D017710:Lymphocyte Transfusion / Q000379:methods; D008297:Male; D008875:Middle Aged; D012190:Retroviridae / Q000235:genetics; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome; D014430:Twins, Monozygotic