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AIDS Res Hum Retroviruses. 2018 Jan;34(1):111-122. doi: 10.1089/aid.2017.0071. Epub 2017 Jun 21.

Immunogenicity of AGS-004 Dendritic Cell Therapy in Patients Treated During Acute HIV Infection.

Author information

1
1 University of North Carolina HIV Cure Center , Chapel Hill, North Carolina.
2
2 Department of Medicine, University of North Carolina Chapel Hill , Chapel Hill, North Carolina.
3
3 Argos Therapeutics , Durham, North Carolina.
4
4 Department of Epidemiology, University of North Carolina Chapel Hill , Chapel Hill, North Carolina.
5
6 Duke University , Durham, North Carolina.
6
7 National Cancer Institute , Frederick, Maryland.
7
8 Tufts University , Boston, Massachusetts.
8
5 Department of Microbiology and Immunology, University of North Carolina Chapel Hill , Chapel Hill, North Carolina.

Abstract

AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4+ T-cell infection (RCI) was measured by quantitative viral outgrowth assay. Participants demonstrating increased immune response postvaccination were eligible for analytic treatment interruption (ATI). AGS-004 induced a positive immune response defined as ≥2-fold increase from baseline in the number of multifunctional HIV-1 specific CD28+/CD45RA- CD8+ effector/memory cytoxic T-lymphocytes (CTLs) in all six participants. All participants underwent ATI with rebound viremia at a median of 29 days. Immune correlates between time to viral rebound and the induction of effector CTLs were determined. Baseline RCI was low in most participants (0.043-0.767 IUPM). One participant had a >2-fold decrease (0.179-0.067 infectious units per million [IUPM]) in RCI at week 10. One participant with the lowest RCI had the longest ATI. AGS-004 dendritic cell administration increased multifunctional HIV-specific CD28+/CD45RA- CD8+ memory T cell responses in all participants, but did not permit sustained ART interruption. However, greater expansion of CD28-/CCR7-/CD45RA- CD8+ effector T cell responses correlated with a longer time to viral rebound. AGS-004 may be a useful tool to augment immune responses in the setting of latency reversal and eradication strategies.

KEYWORDS:

HIV; HIV eradication; acute HIV infection; analytic treatment interruption; dendritic cell vaccine

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