The Effects of Human Immunodeficiency Virus Type 1 (HIV-1) Antigen-Expanded Specific T-Cell Therapy and Vorinostat on Persistent HIV-1 Infection in People With HIV on Antiretroviral Therapy

Cynthia L. Gay, UNC HIV Cure Center, University of North Carolina at Chapel Hill.
Patrick J. Hanley, Center for Cancer and Immunology Research, Children's National Health System.
Shane D. Falcinelli, UNC HIV Cure Center, University of North Carolina at Chapel Hill.
JoAnn D. Kuruc, UNC HIV Cure Center, University of North Carolina at Chapel Hill.
Susan M. Pedersen, UNC HIV Cure Center, University of North Carolina at Chapel Hill.
Jennifer Kirchherr, UNC HIV Cure Center, University of North Carolina at Chapel Hill.
Samuel L. Raines, UNC HIV Cure Center, University of North Carolina at Chapel Hill.
Cecilia M. Motta, Center for Cancer and Immunology Research, Children's National Health System.
Chris Lazarski, Center for Cancer and Immunology Research, Children's National Health System.
Pamela Chansky, Center for Cancer and Immunology Research, Children's National Health System.
Jay Tanna, Center for Cancer and Immunology Research, Children's National Health System.
Abeer Shibli, Center for Cancer and Immunology Research, Children's National Health System.
Anushree Datar, Center for Cancer and Immunology Research, Children's National Health System.
Chase D. McCann, Center for Cancer and Immunology Research, Children's National Health System.
Uluhan Sili, Center for Cancer and Immunology Research, Children's National Health System.
Ruian Ke, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, New Mexico.
Joseph J. Eron, UNC HIV Cure Center, University of North Carolina at Chapel Hill.
Nancie Archin, UNC HIV Cure Center, University of North Carolina at Chapel Hill.
Nilu Goonetilleke, UNC HIV Cure Center, University of North Carolina at Chapel Hill.
Catherine M. Bollard, Center for Cancer and Immunology Research, Children's National Health System.
David M. Margolis, UNC HIV Cure Center, University of North Carolina at Chapel Hill.

Document Type

Journal Article

Publication Date

3-14-2024

Journal

The Journal of infectious diseases

Volume

229

Issue

3

DOI

10.1093/infdis/jiad423

Keywords

HIV latency; T-cell therapy; latency reversal

Abstract

BACKGROUND: The histone deacetylase inhibitor vorinostat (VOR) can reverse human immunodeficiency virus type 1 (HIV-1) latency in vivo and allow T cells to clear infected cells in vitro. HIV-specific T cells (HXTCs) can be expanded ex vivo and have been safely administered to people with HIV (PWH) on antiretroviral therapy. METHODS: Six PWH received infusions of 2 × 107 HXTCs/m² with VOR 400 mg, and 3 PWH received infusions of 10 × 107 HXTCs/m² with VOR. The frequency of persistent HIV by multiple assays including quantitative viral outgrowth assay (QVOA) of resting CD4+ T cells was measured before and after study therapy. RESULTS: VOR and HXTCs were safe, and biomarkers of serial VOR effect were detected, but enhanced antiviral activity in circulating cells was not evident. After 2 × 107 HXTCs/m² with VOR, 1 of 6 PWH exhibited a decrease in QVOA, and all 3 PWH exhibited such declines after 10 × 107 HXTCs/m² and VOR. However, most declines did not exceed the 6-fold threshold needed to definitively attribute decline to the study intervention. CONCLUSIONS: These modest effects provide support for the strategy of HIV latency reversal and reservoir clearance, but more effective interventions are needed to yield the profound depletion of persistent HIV likely to yield clinical benefit. Clinical Trials Registration. NCT03212989.

Department

Pediatrics

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