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

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.