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

• Published in: Molecular therapy. Methods & clinical development Vol. 15; pp. 9 - 17
• Main Authors: Xu, Yinyan, Trumble, Ilana M., Warren, Joanna A., Clutton, Genevieve, Abad-Fernandez, Maria, Kirchnerr, Jennifer, Adimora, Adaora A., Deeks, Steven G., Margolis, David M., Kuruc, JoAnn D., Gay, Cynthia L., Archin, Nancie M., Mollan, Katie R., Hudgens, Michael, Goonetilleke, Nilu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13-12-2019; Elsevier Limited; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Acquired immune deficiency syndrome; Age; AIDS; Antiretroviral drugs; Antiretroviral therapy; CD8; Cell size; Clinical trials; Drug therapy; Enzyme-linked immunosorbent assay; Ethnicity; Hispanic Americans; HIV; Human immunodeficiency virus; Immunotherapy; Infections; Interferon; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Peptides; Peripheral blood mononuclear cells; Proteins; T cell; Vaccines; Viremia; HIV; T cell; CD8; immunotherapy
• ISSN: 2329-0501; 2329-0501
• DOI: 10.1016/j.omtm.2019.07.008

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.