title: Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
abstract: BACKGROUND
  The genomic heterogeneity of HIV-1 impedes the ability of consensus sequences in vaccines to elicit effective antiviral immune responses. AGS-004 amplifies translation-competent RNA molecules encoding for Gag, Rev, Vpr, and Nef from the patient's autologous virus and loads them into dendritic cells.
  
  
  METHODS
  This phase IIB, multicenter, 2:1 randomized, double-blind, placebo-controlled study enrolled 54 HIV-1-infected patients on antiretroviral therapy with viral loads (VLs) <50 copies per milliliter, current CD4 T-cell counts >450 cells per cubic millimeter, and nadir counts >200 cells per cubic millimeter, to receive intradermal injections of study product into the axillary lymph node region every 4 weeks. At week 16, a 12-week analytical treatment interruption (ATI) was undertaken.
  
  
  RESULTS
  There was no difference in the end-of-ATI VL (average of values from weeks 11 and 12) between the 2 arms of the study [4.39 (4.17, 4.69) vs. 4.47 (3.76, 4.64) log10 HIV-1 RNA; P = 0.73]. Between arms, no change between pre-antiretroviral therapy VL and the end-of-ATI VL [-0.06 (0.24, -0.32) vs. -0.17 (0.17, -0.32) log10 HIV-1 RNA; P = 0.43] was observed. When interferon-γ, interleukin-2, tumor necrosis factor α, CD107a, and granzyme b expressions were measured by multicolor flow cytometry, a greater percentage of AGS-004 than of placebo recipients had multifunctional cytotoxic T-lymphocyte responses induced in the CD28+/CD45RA-CD8 effector/memory T-cell population to dendritic cells electroporated with autologous antigens. Adverse events consisted of transient, mild (grade 1) local injection site reactions.
  
  
  CONCLUSIONS
  Despite the induction of HIV-specific effector/memory CD8 T-cell responses, no antiviral effect was seen after the administration of AGS-004 when compared with placebo.
authors.affiliation: *Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA; †Division of Hematology and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada; ‡Department of Epidemiology and Biostatistics, Drexel University College of Medicine, Philadelphia, PA; §Argostherapeutics, Durham, NC; ‖Division of Infectious Diseases, The Ottawa Hospital and the University of Ottawa, Ottawa, CA; ¶Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA; #Department of Medicine, Albert Einstein College of Medicine, New York, NY; **Clinique Medicale du Quartier Latin, Montreal, Quebec, Canada; ††Duke University Medical Center, Durham, NC; ‡‡UNC HIV Cure Center and Departments of Medicine, Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC; §§Clinique Medicale l'Actuel, Montreal, Quebec, Canada; and ‖‖Frontier Science, Amherst, NY.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Seth
authors.initials: S
authors.lastname: Welles
authors.forename: Mark
authors.initials: M
authors.lastname: DeBenedette
authors.forename: Irina
authors.initials: I
authors.lastname: Tcherepanova
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Angel
authors.forename: David M
authors.initials: DM
authors.lastname: Asmuth
authors.forename: David K
authors.initials: DK
authors.lastname: Stein
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Baril
authors.forename: Mehri
authors.initials: M
authors.lastname: McKellar
authors.forename: David M
authors.initials: DM
authors.lastname: Margolis
authors.forename: Benoit
authors.initials: B
authors.lastname: Trottier
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wood
authors.forename: Charles
authors.initials: C
authors.lastname: Nicolette
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000627:therapeutic use; D012367:RNA, Viral / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019562:Viral Load; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D052118:Lysosomal-Associated Membrane Protein 1; D010919:Placebos; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054321:rev Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D007371:Interferon-gamma; D053804:Granzymes