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Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Publication ,  Journal Article
Jacobson, JM; Routy, J-P; Welles, S; DeBenedette, M; Tcherepanova, I; Angel, JB; Asmuth, DM; Stein, DK; Baril, J-G; McKellar, M; Margolis, DM ...
Published in: J Acquir Immune Defic Syndr
May 1, 2016

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.

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Published In

J Acquir Immune Defic Syndr

DOI

EISSN

1944-7884

Publication Date

May 1, 2016

Volume

72

Issue

1

Start / End Page

31 / 38

Location

United States

Related Subject Headings

  • vpr Gene Products, Human Immunodeficiency Virus
  • rev Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus
  • Young Adult
  • Virology
  • Viral Load
  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes, Cytotoxic
  • RNA, Viral
 

Citation

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Jacobson, J. M., Routy, J.-P., Welles, S., DeBenedette, M., Tcherepanova, I., Angel, J. B., … Nicolette, C. (2016). Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Acquir Immune Defic Syndr, 72(1), 31–38. https://doi.org/10.1097/QAI.0000000000000926
Jacobson, Jeffrey M., Jean-Pierre Routy, Seth Welles, Mark DeBenedette, Irina Tcherepanova, Jonathan B. Angel, David M. Asmuth, et al. “Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.J Acquir Immune Defic Syndr 72, no. 1 (May 1, 2016): 31–38. https://doi.org/10.1097/QAI.0000000000000926.
Jacobson JM, Routy J-P, Welles S, DeBenedette M, Tcherepanova I, Angel JB, et al. Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Acquir Immune Defic Syndr. 2016 May 1;72(1):31–8.
Jacobson, Jeffrey M., et al. “Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.J Acquir Immune Defic Syndr, vol. 72, no. 1, May 2016, pp. 31–38. Pubmed, doi:10.1097/QAI.0000000000000926.
Jacobson JM, Routy J-P, Welles S, DeBenedette M, Tcherepanova I, Angel JB, Asmuth DM, Stein DK, Baril J-G, McKellar M, Margolis DM, Trottier B, Wood K, Nicolette C. Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Acquir Immune Defic Syndr. 2016 May 1;72(1):31–38.

Published In

J Acquir Immune Defic Syndr

DOI

EISSN

1944-7884

Publication Date

May 1, 2016

Volume

72

Issue

1

Start / End Page

31 / 38

Location

United States

Related Subject Headings

  • vpr Gene Products, Human Immunodeficiency Virus
  • rev Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus
  • Young Adult
  • Virology
  • Viral Load
  • Tumor Necrosis Factor-alpha
  • T-Lymphocytes, Cytotoxic
  • RNA, Viral