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.
*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.
Correspondence to: Jeffrey M. Jacobson, MD, Professor of Medicine, Microbiology and Immunology, Chief, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, 245 N. 15th Street, MS 461, Philadelphia, PA 19102 (e-mail: email@example.com).
This work was funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. N01-AI-60019; by the Canadian Institutes of Health Research [grants MOP #103230 and CTN #256]; the Canadian HIV Cure Enterprise Team [Grant HIG-133050] (J.-P.R. and J.B.A.) from the CIHR and Fonds de la Recherche Quebec Sante (FRQ-S): Réseau SIDA/Maladies infectieuses. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
M.D., I.T., and C.N. are employees of Argostherapeutics, Inc. (Durham, NC). J.M.J., J.-P.R., and D.M.M. have each received an honorarium from Merck Pharmaceuticals. The other authors have no conflicts of interest to disclose.
Clinical Trials Registry Number: NCT00672191.
Received September 16, 2015
Accepted December 08, 2015