Levels of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte effector and memory responses decline after suppression of viremia withhighly active antiretroviral therapy

Therapeutic suppression of human immunodeficiency virus type 1 (HIV-1) repl ication may help elucidate interactions between the host cellular immune re sponses and HIV-1 infection. We performed a detailed longitudinal evaluatio n of two subjects before and after the start of highly active antiretrovira l therapy (HAART). Both subjects had evidence of in vivo-activated and memo ry cytotoxic T-lymphocyte precursor (CTLp) activity against multiple HIV-1 gene products. After the start of therapy, both subjects had declines in th e levels of in vivo-activated HIV-1-specific CTLs and had immediate increas es in circulating HIV-1-specific CTL memory cells. With continued therapy, and continued suppression of viral load, levels of memory CTLps declined. H LA A*0201 peptide tetramer staining demonstrated that declining levels of i n vivo-activated CTL activity were associated with a decrease in the expres sion of the CD38(+) activation marker. Transient increases in viral load du ring continued therapy were associated with increases in the levels of viru s-specific CTLps in both individuals. The results were confirmed by measuri ng CTL responses to discrete optimal epitopes. These studies illustrate the dynamic equilibrium between the host immune response and levels of viral a ntigen burden and suggest that efforts to augment HIV-1-specific immune res ponses in subjects on HAART may decrease the incidence of virologic relapse .