Short Communication: HIV Rebound after Discontinuation of Antiretroviral Therapy Increases and Expands HIV-Specific CD8 + Responses But Has No Impact on Its Functionality

Abstract

A higher functionality of CD8⁺ T cells might contribute to low-level HIV replication in long-term nonprogressors (LTNPs). However, the contrary could also be true, being the function of CD8⁺ T cells modulated by HIV replication. We tested whether enhanced HIV replication following antiretroviral therapy interruption could modify the functional profile of HIV-specific CD8⁺ responses. Production of MIP-1β, IL-2, TNF-α, and CD107 expression by CD8⁺ T cells in response to Gag and Nef optimal peptide pools was analyzed using polychromatic flow cytometry in nine HIV-infected individuals followed for 12 months after discontinuation of antiretroviral therapy. At baseline, CD8⁺ T cell subsets with the greatest contribution to response were MIP-β ⁺TNF-α ⁻IL-2⁻CD107⁺ and MIP-β ⁺TNF-α ⁻IL-2⁻CD107. Most responses were mediated by subsets expressing only one or two molecules. After 12 months of discontinuing antiretroviral therapy, no significant differences were observed in the functional profile of Gag- and Nef-specific CD8⁺ responses. However, viral rebound induced a significant increase in the heterogeneity of Gag-specific CD8⁺ responses. In summary, viral replication following discontinuation of antiretroviral therapy has no significant impact on qualitative aspects of HIV-specific CD8⁺ responses. Thus, a higher functionality of CD8⁺ responses does not seem to be the consequence of low-level virus replication.