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 language | English (US) |
|---|---|
| Journal | Journal of Acquired Immune Deficiency Syndromes |
| DOIs | |
| State | Accepted/In press - Jan 8 2016 |
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ASJC Scopus subject areas
- Infectious Diseases
- Pharmacology (medical)
Cite this
Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA : A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. / Jacobson, Jeffrey M.; Routy, Jean Pierre; Welles, Seth; DeBenedette, Mark; Tcherepanova, Irina; Angel, Jonathan B.; Asmuth, David; Stein, David K.; Baril, Jean Guy; McKellar, Mehri; Margolis, David M.; Trottier, Benoit; Wood, Kenneth; Nicolette, Charles.
In: Journal of Acquired Immune Deficiency Syndromes, 08.01.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dendritic Cell Immunotherapy for HIV-1 Infection Using Autologous HIV-1 RNA
T2 - A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
AU - Jacobson, Jeffrey M.
AU - Routy, Jean Pierre
AU - Welles, Seth
AU - DeBenedette, Mark
AU - Tcherepanova, Irina
AU - Angel, Jonathan B.
AU - Asmuth, David
AU - Stein, David K.
AU - Baril, Jean Guy
AU - McKellar, Mehri
AU - Margolis, David M.
AU - Trottier, Benoit
AU - Wood, Kenneth
AU - Nicolette, Charles
PY - 2016/1/8
Y1 - 2016/1/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84954509568&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84954509568&partnerID=8YFLogxK
U2 - 10.1097/QAI.0000000000000926
DO - 10.1097/QAI.0000000000000926
M3 - Article
C2 - 26751016
AN - SCOPUS:84954509568
JO - Journal of acquired immune deficiency syndromes (1999)
JF - Journal of acquired immune deficiency syndromes (1999)
SN - 1525-4135
ER -