Lymphocyte kinetics and precursor frequency-dependent recovery of CD4+CD45RA+CD62L+ naive T cells following triple-drug therapy for HIV type 1 infection

New therapeutic regimens have dramatically altered morbidity and mortality attributed to HIV-1 infection. Changes in lymphocyte subsets after treatment may mirror salutary clinical changes. Over 4 months we analyzed lymphocyte subsets in 20 patients starting new HIV-1 therapy. Absolute numbers of lymphocytes, CD4+ T cells, CD8+ T cells, and B cells increased significantly by 4 months, but CD8+ T cell and B cell increases were restricted to late-stage patients. Subset analysis revealed that the magnitude of recovering naive-phenotype CD4+ T cells (slope) correlated with the number of these cells present at baseline, equaling or exceeding the memory-phenotype slope within days if these naive cells were abundant at baseline. Five of 10 patients in whom naive-phenotype CD4+ T cells were absent at baseline partially repopulated these cells by 4 months. These findings have important implications for the origin and mechanisms of renewal of naive-phenotype CD4+ T cells following effective treatment for HIV-1 infection.