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Journal article
Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, v 72(1), pp 31-38
01 May 2016
PMID: 26751016
Featured in Collection : UN Sustainable Development Goals @ Drexel
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) log(10) 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) log(10) HIV-1 RNA; P = 0.43] was observed. When interferon-g, interleukin-2, tumor necrosis factor alpha, 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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Details
- Title
- Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
- Creators
- Jeffrey M. Jacobson - Drexel UniversityJean-Pierre Routy - McGill UniversitySeth Welles - Drexel UniversityMark DeBenedette - §Argostherapeutics, Durham, NCIrina Tcherepanova - University of OttawaJonathan B. Angel - Ottawa HospitalDavid M. Asmuth - University of California Davis Medical CenterDavid K. Stein - Albert Einstein College of MedicineJean-Guy Baril - Duke Medical CenterMehri McKellar - Duke UniversityDavid M. Margolis - University of North Carolina at Chapel HillBenoit Trottier - Frontier Science FoundationKenneth Wood - Frontier Science & Technology Research FoundationCharles Nicolette - Ottawa Hospital
- Publication Details
- JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, v 72(1), pp 31-38
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 8
- Grant note
- 103230; 256 / Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) N01-AI-60019 / National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) HIG-133050 / Canadian HIV Cure Enterprise Team from the CIHR Fonds de la Recherche Quebec Sante (FRQ-S): Reseau SIDA/Maladies infectieuses P30AI064518 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000375067600014
- Scopus ID
- 2-s2.0-84954509568
- Other Identifier
- 991019167619004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases