Use of Well-Defined HIV-Derived Epitopes to Evaluate CD4 + and CD8 + T Cell Responses in Patients with Chronic HIV-1 Infection Treated with HAART

Abstract

Highly active antiretroviral therapy (HAART) is associated with a dramatic clinical benefit to HIV-infected patients through significant plasma viremia reduction and CD4⁺ T cells increase. In previous reports, HIV-specific CD4⁺ and/or CD8⁺ T cell responses have been studied separately during HAART; therefore the relationship between these two virus-specific populations is currently not well understood. In this study, both HIV-specific CD4⁺ and CD8⁺ T cell responses were investigated using a large panel of well-defined T cell epitope peptides in 24 HIV-1-infected patients undergoing HAART, with undetectable viral load and CD4⁺ T cell count ≥ 350/mm³. One-third of the patients had CD4⁺ T cells able to proliferate when exposed to HIV-1 protein fragments but only two patients displayed polyclonal responses. In addition the majority (78%) of HAART-treated patients displayed no or monospecific CD8⁺ T cell responses and the phenotypic analysis of these HIV-specific CD8⁺ T cells demonstrated the absence of terminally differentiated effectors. In conclusion, the experimental approach used in this study shows that CD4⁺ T cell responses may persist during HAART but are not associated with strong CD8⁺ T cell responses