Human immunodeficiency virus type I-specific CD8+ T cell subset abnormalities in chronic infection persist through effective antiretroviral therapy

Background: Effective highly active antiretroviral therapy (HAART) reduces human immunodeficiency virus (HIV) replication, restores CD4(+) T lymphocyte counts and greatly reduces the incidence of opportunistic infections. While this demonstrates improved generalized immune function, rapid rebound to pre-treatment viral replication levels following treatment interruption indicates little improvement in immune control of HIV replication. The extent to which HAART can normalize HIV-specific CD8(+) T cell function over time in individuals with chronic infection remains an important unresolved issue. In this study, we evaluated the magnitude, general specificity and character of HIV specific CD8(+) T cell responses at four time points across 2-9 years in 2 groups of chronically infected individuals separated on the basis of either effective antiretroviral suppression or ongoing replication of HIV. Methods: Peripheral blood mononuclear cells (PBMC) were stimulated with overlapping 15mer peptides spanning HIV Gag, Pol, Env and Nef proteins. Cells producing interferon-gamma (IFN-gamma) or interleukin-2 (IL-2) were enumerated by ELISPOT and phenotyped by flow cytometry. Results and Conclusions: The magnitude of the HIV-specific CD8(+) T cell response ranged from < .01 to approximately 1.0% of PBMC and was significantly greater in the group with detectable viral replication. Stronger responses reflected higher numbers of CD8(+)CD45RA(-) effector memory cells producing IFN-gamma, but not IL-2. Magnitude, general specificity and character of the HIV-specific CD8(+) T cell response changed little over the study period. While antiretroviral suppression of HIV in chronic infection reduces HIV-specific CD8(+) T cell response magnitude in the short term, it had no significant effect on response character over periods up to 9 years.