Improved CD4 lymphocyte outgrowth in response to effective antiretroviral therapy

CD4 lymphocyte regenerative capacity was evaluated by use of an ex vivo out growth assay in human immunodeficiency virus (HIV)-1-infected subjects enro lled in a clinical trial (Merck 039), CD4 lymphocytes were selectively expa nded in vitro by T cell receptor triggering, which also induces HIV product ion from latently infected cells. CD4 cell expansion and lack of virus prod uction in cultures correlated well with clinical responses and were best in those receiving an aggressive antiretroviral three-drug regimen. Twelve cl inical responders receiving triple-drug therapy monitored for 60 weeks had both excellent ex vivo CD4 cell expansion and lack of HIV replication, ofte n in the absence of added drug in culture. Breakthrough viruses recovered f rom drug-containing arms of the cultures showed phenotypic resistance to th e drugs used in vivo. This CD4 lymphocyte outgrowth assay correlates well w ith clinical outcome in subjects receiving potent antiretroviral regimens a nd may predict the emergence of early drug resistance.