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

Jeffrey M. Jacobson, Jean Pierre Routy, Seth Welles, Mark DeBenedette, Irina Tcherepanova, Jonathan B. Angel, David Asmuth, David K. Stein, Jean Guy Baril, Mehri McKellar, David M. Margolis, Benoit Trottier, Kenneth Wood, Charles Nicolette

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27 Scopus citations

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 (DC). METHODS:: This phase IIB, multicenter, 2:1 randomized, double blind, placebo-controlled study enrolled 54 HIV-1-infected patients on antiretroviral therapy (ART) with viral loads (VL) 450 cells/mm, and nadir counts >200 cells/mm, 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 two 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-ART 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 IFN-γ, IL-2, TNF-α, CD107a, and granzyme b expression was measured by multicolor flow cytometry, a greater percentage of AGS-004 than of placebo recipients had multifunctional CTL responses induced in the CD28+/CD45RA- CD8 effector/memory T-cell population to DCs 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 to placebo.

Original languageEnglish (US)
JournalJournal of Acquired Immune Deficiency Syndromes
DOIs
StateAccepted/In press - Jan 8 2016

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ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Jacobson, J. M., Routy, J. P., Welles, S., DeBenedette, M., Tcherepanova, I., Angel, J. B., Asmuth, D., Stein, D. K., Baril, J. G., McKellar, M., Margolis, D. M., Trottier, B., Wood, K., & Nicolette, C. (Accepted/In press). Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Journal of Acquired Immune Deficiency Syndromes. https://doi.org/10.1097/QAI.0000000000000926