Blood biomarkers of expressed and inducible HIV-1

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 DNArho = 0.64, P = 0.0017; unspliced HIV-1 RNArho = 0.77, P