title: Safety of autologous, ex vivo-expanded human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients.
abstract: We infused six human immunodeficiency virus (HIV)-seropositive subjects with autologous CD8+ cytotoxic T cells (CTLs) enriched for HIV-specific cytotoxicity targeted against a diversity of HIV epitopes in gp120, gag p17 and p24, and nef. There was no toxicity and no subject deteriorated clinically. In the first 2 weeks, CD4 counts increased for all subjects and plasma viremia decreased in five of six subjects. Twenty-four weeks later, the mean values of all measures of viral burden and surrogate markers of HIV infection were either unchanged or improved, but none of the changes was statistically significant. Two subjects continued to have decreased cell-associated viral burden and another subject had more than doubled CD4 cell count. HIV-specific CTL activity increased in most subjects. The increase in CD4 T-cell counts in the first weeks after the infusion suggests that antiviral CTLs of diverse specificities do not play a significant role in CD4 T-cell decline. The lack of any acute toxicity or adverse effect on viral burden suggests that therapy with antiviral CTLs deserves further study.
authors.affiliation: Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lieberman
authors.forename: P R
authors.initials: PR
authors.lastname: Skolnik
authors.forename: G R
authors.initials: GR
authors.lastname: Parkerson
authors.forename: J A
authors.initials: JA
authors.lastname: Fabry
authors.forename: B
authors.initials: B
authors.lastname: Landry
authors.forename: J
authors.initials: J
authors.lastname: Bethel
authors.forename: J
authors.initials: J
authors.lastname: Kagan
mesh_terms: D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D015693:Gene Products, nef / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007167:Immunotherapy / Q000379:methods; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D010865:Pilot Projects; D013602:T-Lymphocytes, Cytotoxic / Q000637:transplantation*; D014764:Viral Proteins / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D010455:Peptides; D014764:Viral Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus