Evaluation of distinct blood lymphocyte populations in human immunodeficiency virus type 1-infected subjects in the absence or presence of effective therapy

Virus reservoirs can persist in human immunodeficiency virus type 1 (HIV-l) -infected subjects despite effective plasma virus suppression, To compare v iral dynamics in the absence and presence of antiretroviral therapy, blood mononuclear cells from 19 subjects with high plasma RNA levels and 18 subje cts following prolonged virus suppression were examined, by use of in situ hybridization, to detect virus RNA expression before and after in vitro T c ell activation. This approach reveals circulating lymphocytes expressing HI V-1 RNA before activation and an increase in cells with detectable HIV-1 RN A transcription after in vitro activation. The frequencies of these 2 cell populations are strongly correlated with plasma virus load and appear to be stable once a new steady state is established during therapy. The frequenc y of viral RNA-positive cells is equivalent to the frequency of cells that produce infectious virus. Thus, in HIV-l-infected subjects there are distin ct virus reservoirs comprising both latent and replication-active cells.