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- Title
Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat on persistent HIV-1 Infection.
- Authors
Gay, Cynthia L.; Kuruc, Joann D.; Falcinelli, Shane D.; Warren, Joanna A.; Reifeis, Sarah A.; Kirchherr, Jennifer L.; James, Katherine S.; Dewey, Morgan G.; Helms, Alyson; Allard, Brigitte; Stuelke, Erin; Gamble, Alicia; Plachco, Ana; Gorelick, Robert J.; Eron, Joseph J.; Hudgens, Michael; Garrido, Carolina; Goonetilleke, Nilu; DeBenedette, Mark A.; Tcherepanova, Irina Y.
- Abstract
Approaches to deplete persistent HIV infection are needed. We investigated the combined impact of the latency reversing agent vorinostat (VOR) and AGS-004, an autologous dendritic cell immunotherapeutic, on the HIV reservoir. HIV+, stably treated participants in whom resting CD4+ T cell-associated HIV RNA (rca-RNA) increased after VOR exposure ex vivo and in vivo received 4 doses of AGS-004 every 3 weeks, followed by VOR every 72 hours for 30 days, and then the cycle repeated. Change in VOR-responsive host gene expression, HIV-specific T cell responses, low-level HIV viremia, rca-RNA, and the frequency of resting CD4+ T-cell infection (RCI) was measured at baseline and after each cycle. No serious treatment-related adverse events were observed among five participants. As predicted, VOR-responsive host genes responded uniformly to VOR dosing. Following cycles of AGS-004 and VOR, rca-RNA decreased significantly in only two participants, with a significant decrease in SCA observed in one of these participants. However, unlike other cohorts dosed with AGS-004, no uniform increase in HIV-specific immune responses following vaccination was observed. Finally, no reproducible decline of RCI, defined as a decrease of >50%, was observed. AGS-004 and VOR were safe and well-tolerated, but no substantial impact on RCI was measured. In contrast to previous clinical data, AGS-004 did not induce HIV-specific immune responses greater than those measured at baseline. More efficacious antiviral immune interventions, perhaps paired with more effective latency reversal, must be developed to clear persistent HIV infection.
- Subjects
DENDRITIC cells; IMMUNOTHERAPY; HIV infections; VIRAL latency-associated transcript protein; GENE expression in mammals; T cells
- Publication
Scientific Reports, 2020, Vol 10, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-020-61878-3