Influence of HIV Infection on Cytomegalovirus-Specific Immunity: T-Cell Responses to Pp65 and Ie1 before and after Haart May Refect Altered Cytomegalovirus Biology

Abstract

Data are inconclusive whether treatment with HAART induces functional recovery of HIV-specific T-cells. Since the introduction of HAART, a marked decrease of cytomegalovirus (CMV) disease - for which untreated HIV-infected individuals are at increased risk - is observed, suggesting that this treatment influences CMV-specific T-cell immunity. To study potential functional recovery of HIV- and CMV-specific T-cells, CD4(+) and CD8(+) T-cell responses were measured longitudinally after in vitro expansion using gag, pp65 and IE1 peptide pools, during HIV infection and after long-term HAART. HIV-specific T-cell function, measured by interferon (IFN)-γ production, was low after initiation of HAART. Interestingly, the cytotoxic function - measured by CD107a expression - of these T-cells temporarily increased after start of treatment, suggesting some functional recovery. The pp65-specific CD8(+) T-cell responses tended to decrease during HIV infection, whereas pp65-specific CD4(+) T-cell responses decreased upon treatment with HAART. Both pp65-specific CD4(+) and CD8(+) T-cell responses were low after initiation of HAART compared to healthy controls. By contrast, IE1-specific CD4(+) T-cell responses increased during the course of HIV infection. After initiation of HAART, IE1-specific T-cell responses decreased, but IE1-specific CD8(+) T-cells seemed increased compared to healthy controls. This study suggests that HIV-infection leads to an altered CMV biology, affecting pp65- and IE1-specific T-cell responses in a different way, which is not restored by treatment with long-term HAART.