| Autor: |
Gorelick, R.J., Margolis, D.M., Reifeis, S.A., Kuruc, J.D., Warren, J.A., Hudgens, M., Gay, C.L., Dewey, M.G., Allard, B., Goonetilleke, N., Falcinelli, S.D., Gamble, A., James, K.S., Stuelke, E., Tcherepanova, I.Y., Kirchherr, J.L., Plachco, A., Archin, N.M., Eron, J.J., DeBenedette, M.A., Garrido, C., Nicolette, C.A., Helms, A. |
| Předmět: |
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| Popis: |
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. |
| Databáze: |
OpenAIRE |
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