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[PMID]: | 26751016 |
[Au] Autor: | Jacobson JM; Routy JP; Welles S; DeBenedette M; Tcherepanova I; Angel JB; Asmuth DM; Stein DK; Baril JG; McKellar M; Margolis DM; Trottier B; Wood K; Nicolette C |
[Ad] Endereço: | *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. |
[Ti] Título: | Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. |
[So] Source: | J Acquir Immune Defic Syndr;72(1):31-8, 2016 May 01. | [Is] ISSN: | 1944-7884 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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. |
[Mh] Termos MeSH primário: |
Células Dendríticas/imunologia Infecções por HIV/terapia HIV-1/imunologia Imunoterapia/métodos RNA Viral/uso terapêutico Linfócitos T Citotóxicos/imunologia
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[Mh] Termos MeSH secundário: |
Adolescente Adulto Contagem de Linfócito CD4 Linfócitos T CD4-Positivos/imunologia Método Duplo-Cego Feminino Granzimas/biossíntese HIV-1/genética Seres Humanos Interferon gama/biossíntese Interleucina-2/biossíntese Proteína 1 de Membrana Associada ao Lisossomo/biossíntese Masculino Meia-Idade Placebos/uso terapêutico Fator de Necrose Tumoral alfa/biossíntese Carga Viral Adulto Jovem Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética Produtos do Gene rev do Vírus da Imunodeficiência Humana/genética Produtos do Gene vpr do Vírus da Imunodeficiência Humana/genética
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[Pt] Tipo de publicação: | CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (IL2 protein, human); 0 (Interleukin-2); 0 (Lysosomal-Associated Membrane Protein 1); 0 (Placebos); 0 (RNA, Viral); 0 (Tumor Necrosis Factor-alpha); 0 (gag Gene Products, Human Immunodeficiency Virus); 0 (nef Gene Products, Human Immunodeficiency Virus); 0 (nef protein, Human immunodeficiency virus 1); 0 (rev Gene Products, Human Immunodeficiency Virus); 0 (vpr Gene Products, Human Immunodeficiency Virus); 0 (vpr protein, Human immunodeficiency virus 1); 82115-62-6 (Interferon-gamma); EC 3.4.21.- (Granzymes) |
[Em] Mês de entrada: | 1609 |
[Cu] Atualização por classe: | 170501 |
[Lr] Data última revisão:
| 170501 |
[Sb] Subgrupo de revista: | IM; X |
[Da] Data de entrada para processamento: | 160112 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1097/QAI.0000000000000926 |
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