A significant percentage of human immunodeficiency virus type 1 (HIV-1)–infected persons treated with highly active antiretroviral therapy (HAART) will develop plasma HIV-1–specific virion RNA levels <50 copies/mL. HIV-1–infected persons receiving virally suppressive HAART were studied with a viral outgrowth assay of the patients’ peripheral blood mononuclear cells (PBMC), and a quantitative polymerase chain reaction assay was used to analyze HIV-1 2–long terminal repeat (2-LTR) circular DNA in PBMC, which indicates new HIV-1 infections of cells in vivo. Viral outgrowth in vitro correlated inversely with the level of peripheral blood CD4+ T lymphocytes. Detection and quantitation of 2-LTR circular DNA correlated strongly with viral outgrowth patterns and inversely with CD4+ T lymphocyte counts. Relevant subgroups of HIV-1–infected subjects on suppressive HAART with residual viral disease and reservoirs can now be stratified