KINETICS OF CD4-CELL REPOPULATION OF LYMPHOID-TISSUES AFTER TREATMENTOF HIV-1 INFECTION( T)

Potent combinations of antiretroviral drugs diminish the turnover of C D4+ T lymphocytes productively infected with HIV-1 and reduce the larg e pool of virions deposited in lymphoid tissue (LT), To determine to w hat extent suppression of viral replication and reduction in viral ant igens in LT might lead correspondingly to repopulation of the immune s ystem, we characterized CD4+ T lymphocyte populations in LT in which w e previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative imag e analysis changes in total CD4+ T cell counts, the CD45RA+ subset, an d fractions of proliferating or apoptotic CD4+ T cells, Compared with normal controls, we documented decreased numbers of CD4+ T cells and i ncreased proliferation and apoptosis. After treatment, proliferation r eturned to normal levels, and total CD4+ T and CD45RA+ cells increased , We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity be fore infection and cannot meet the additional demand imposed by the lo ss of productively infected cells, The slow increases in the CD45RA+ C D4+ T cells are consistent with the optimistic conclusions that (i) re newal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be p artially restored by control of active replication without eradication of HIV-1.