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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gay, CL; DeBenedette, MA; Tcherepanova, IY; Gamble, A; Lewis, WE; Cope, AB; Kuruc, JD; McGee, KS; Kearney, MF; Coffin, JM; Archin, NM; Hicks, CB; Eron, JJ; Nicolette, CA; Margolis, DM

Published Date

  • January 2018

Published In

Volume / Issue

  • 34 / 1

Start / End Page

  • 111 - 122

PubMed ID

  • 28636433

Pubmed Central ID

  • 28636433

Electronic International Standard Serial Number (EISSN)

  • 1931-8405

International Standard Serial Number (ISSN)

  • 0889-2229

Digital Object Identifier (DOI)

  • 10.1089/aid.2017.0071

Language

  • eng