Blood biomarkers of expressed and inducible HIV-1. (27th March 2018)

• Record Type: Journal Article
• Authors: Cillo, Anthony R.; Hong, Francis; Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Sloan, Derek D.; Follen, Mattie; Geleziunas, Romas; Cihlar, Tomas; Win, Sandra S.; Murry, Jeffrey P.; Mellors, John W.
• Is Part Of: AIDS. Volume 32:Number 6(2018)
• Publication Date: 2018-03-27
• Subjects: biomarkers of HIV persistence -- HIV persistence -- HIV reservoirs -- persistent HIV viremia -- suppressive antiretroviral therapy; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001748
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objective: To define the relationships between molecular measures of viral persistence in blood (i.e., plasma viremia, cellular HIV-1 DNA, and mRNA) and expressed or inducible virus from resting CD4 + T cells of individuals on suppressive antiretroviral therapy. Design: We compared molecular measurements of HIV-1 in plasma and in uncultured peripheral blood mononuclear cells (PBMCs) to the levels of virions produced by either unstimulated or phorbol myristate acetate and ionomycin (PMA/iono)-stimulated PBMC or resting CD4 + T cells from 21 donors on suppressive antiretroviral therapy. Results: We found that unstimulated virion release from cultured resting CD4 + T cells was positively correlated with the levels of plasma viremia in vivo (Spearman rho = 0.67, P = 0.0017). We also found that levels of both cellular HIV-1 DNA and unspliced HIV-1 mRNA per million uncultured PBMC were positively correlated with the levels of inducible virion release from both PMA/iono-stimulated PBMC (total HIV-1 DNA: rho = 0.64, P = 0.0017; unspliced HIV-1 RNA: rho = 0.77, P < 0.001) and PMA/iono-stimulated resting CD4 + T cells (total HIV-1 DNA: rho = 0.75, P < 0.001; unspliced HIV-1 RNA: rho = 0.75, P < 0.001). Conclusion: These results show for the first time that there are strong associations between in-vivo measures of HIV-1 persistence and ex-vivo measures of spontaneous and inducible virus production from cultured PBMC and resting CD4 + T cells. Findings from this study provide insight into the biology of HIV-1 persistence and suggest methods to guide the evaluation of clinical strategies to reduce the size of the viral reservoir. Abstract : Supplemental Digital Content is available in the text