Close link between CD4+ and CD8+ T cell proliferation defects in patients with human immunodeficiency virus disease and relationship to extended periods of CD4+ lymphopenia

T cell proliferation failure is commonly associated with human immunodeficiency virus (HIV) infection. By examining T cell function on a single-cell basis, we found that CD4(+) T cell proliferation failure was often accompanied by CD8(+) T cell proliferation defects in patients with HIV disease. The defects are characterized by a proportional failure and reduced efficiency of precursor T cell proliferation after stimulation. In this study, patients who historically had low levels of circulating CD4(+) T cells were most likely to demonstrate cellular proliferation failure, regardless of current CD4(+) T cell counts. In contrast, neither historical nor current plasma HIV RNA levels were predictive of proliferation failure. These results suggest that mechanisms of T cell proliferation failure are more complex than can be explained by the direct effects of HIV replication and that therapeutic intervention to avoid prolonged periods of CD4(+) lymphopenia may be desirable for the preservation of immune function in patients with HIV disease.