HIV-Specific T Cell Responses Are Highly Stable on Antiretroviral Therapy

Autor: Yinyan Xu, Ilana M. Trumble, Joanna A. Warren, Genevieve Clutton, Maria Abad-Fernandez, Jennifer Kirchnerr, Adaora A. Adimora, Steven G. Deeks, David M. Margolis, JoAnn D. Kuruc, Cynthia L. Gay, Nancie M. Archin, Katie R. Mollan, Michael Hudgens, Nilu Goonetilleke
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Molecular Therapy: Methods & Clinical Development, Vol 15, Iss , Pp 9-17 (2019)
Druh dokumentu: article
ISSN: 2329-0501
DOI: 10.1016/j.omtm.2019.07.008
Popis: HIV infection induces a robust T cell response that is sustained by high viremia, but falls following the onset of antiretroviral therapy (ART). Relatively little has been reported on the subsequent stability of the HIV-specific T cell response in individuals on durable therapy. Such data are critical for powering clinical trials testing T cell-based immunotherapies. In a cross-sectional study, HIV-specific T cell responses were detectable by ex vivo interferon (IFN)-γ ELISpot (average ∼1,100 spot-forming units [SFUs]/106 peripheral blood mononuclear cells) in persons living with HIV (PLWH; n = 34), despite median durable ART suppression of 5.0 years. No substantial association was detected between the summed HIV-specific T cell response and the size of the replication-competent HIV reservoir. T cell responses were next measured in participants sampled weekly, monthly, or yearly. HIV-specific T cell responses were highly stable over the time periods examined; within-individual variation ranged from 16% coefficient of variation (CV) for weekly to 27% CV for yearly sampling. These data were used to generate power calculations for future immunotherapy studies. The stability of the HIV-specific T cell response in suppressed PLWH will enable powered studies of small sizes (e.g., n = 6–12), facilitating rapid and iterative testing for T cell-based immunotherapies against HIV. Keywords: HIV, T cell, immunotherapy, CD8
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