Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV-specific CD8(+) T cells

Abstract

A better control of viral replication in long-term non-progressors has been associated with polyfunctional CD8(+) T cell responses. However, low levels of HIV replication could be the cause rather than the consequence of enhanced immune responses in long-term non-progressors. The functional profile and the expansion ability of HIV-Gag- and HIV-Nef-specific CD8 responses were analysed measuring the production of MIP-1beta, IL-2, TNF-alpha and expression of CD107, using polychromatic flow cytometry, in 36 HIV-infected patients at baseline and after 12 months of highly active antiretroviral therapy (HAART) and complete viral suppression. Most patients presented detectable Gag and Nef responses both at baseline and after 1 year of HAART, with a significant decline after achieving viral suppression. At baseline, the majority of CD8(+) response was due to cells producing only MIP-1beta or simultaneously MIP-1beta and CD107. The functional profile did not significantly change after achieving complete viral suppression with HAART. Therefore, control of HIV-1 replication after 1 year of HAART had no significant impact on the quality of HIV-1-specific CD8 response, but the effects of treatment in long-term, or of early HAART are not known. Thus, it is still uncertain whether multifunctional CD8 responses are the cause or consequence of low plasma viremia.