Immunology, 2Division of Infectious Diseases, Tropical Medicine, and

Lymphoproliferative responses (LPRs) to recall antigens (Ags) and human immunode®-ciency virus type 1 (HIV-1) Gag and frequencies of circulating HIV-1±speci®c cytotoxic T lymphocyte precursors (CTLps) were measured in 12 patients undergoing highly active an-tiretroviral therapy (HAART) after long-standing HIV-1 infection. LPRs to at least 1 recall Ag became detectable or increased in all patients during HAART. No signi®cant LPRs to Gag-p24 were observed, whereas 4 of 8 patients tested presented with Gag-p17±speci®c LPRs. HIV-1±speci®c CTLp frequencies became measurable or increased early during therapy in 6 of 10 patients tested and were maintained or decreased thereafter. Increasing HIV-1±speci®c CTLp frequencies were seen only in association with partial HAART failure in 1 patient. In conclusion, restoration of CD4+ T lymphocyte responsiveness to recall Ags is achieved during HAART. The data provide evidence for limited HIV-1±speci®c CD4+ memory T cells during advanced HIV-1 infection and suggest that both CD4+ and CD8+ HIV-1±speci®c T cells are poorly stimulated when viral load is suppressed. Current antiretroviral therapy (ART) has greatly modi®ed the poor prognosis of human immunode®ciency virus type