Presence of HIV-specific CD4+ T-cell responses in HIV-infected subjects with sustained virologic control after highly active antiretroviral therapy.

HIV-specific CD4+ T-helper cell responses in 40 subjects with chronic infection (CI) who had virus suppression after highly active antiretroviral therapy (HAART) were compared with those in 34 subjects treated during primary infection (PI). A CD4+ T-cell proliferative response to HIV p24 protein was present in 50% of these subjects compared with 79% of subjects treated during PI. The existence of a proliferative response in CI subjects was associated with a higher CD4+ T-cell count at initiation of HAART, a longer duration of virus suppression, and a higher CD4+ T-cell count at the time of analysis. These results show that an HIV-specific proliferative response is preferentially observed in treated CI subjects with CD4+ T-cell counts of >200/microL. However, in treated CI subjects with a significant degree of CD4+ T-cell depletion (<200/microL), it may also be observed in 35% provided that the duration of virus suppression is long enough, which may have implications for future therapeutic strategies.

Impact of antiretroviral therapy and changes in virus load on human immunodeficiency virus (HIV)-specific T cell responses in primary HIV infection.

Human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T cell responses were evaluated prospectively in a large cohort of subjects with HIV primary infection via long-term follow-up examining different virological profiles related to different treatment interventions. No correlation was observed between baseline virus load and HIV-specific CD4(+) and CD8(+) T cell responses. Highly active antiretroviral therapy (HAART)-induced suppression of viremia was associated with an increase in CD4(+) T cell proliferative responses. The HIV-specific proliferative response also increased, at least in the first 18 months, in subjects with detectable viremia, either treated or untreated. The magnitude of the HIV-specific CD8(+) T cell response decreased with suppression of viremia. In subjects with detectable viremia, the breadth and magnitude of the HIV-specific CD8(+) T cell responses increased progressively. Finally, whether HAART was initiated before or after seroconversion had little effect on HIV-specific CD4(+) and CD8(+) T cell responses.

CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection.

Primary viral infections, including primary HIV infection, trigger intense activation of the immune system, with marked expansion of CD38(+)CD8(+) T cells. Whether this expansion involves only viral-specific cells or includes a degree of bystander activation remains a matter of debate. We therefore examined the activation status of EBV-, CMV-, and influenza virus (FLU)-specific CD8(+) T cells during primary HIV infection, in comparison to HIV-specific CD8(+) T cells. The activation markers CD38 and HLA-DR were strongly expressed on HIV-specific CD8(+) T cells. Surprisingly, CD38 expression was also up-regulated on CD8(+) T cells specific for other viruses, albeit to a lesser extent. Activation marker expression returned to normal or near-normal values after 1 year of highly active antiretroviral therapy. HIV viral load correlated with CD38 expression on HIV-specific CD8(+) T cells but also on EBV-, CMV-, and FLU-specific CD8(+) T cells. In primary HIV infection, EBV-specific CD8(+) T cells also showed increased Ki67 expression and decreased Bcl-2 expression, compared with values observed in HIV-seronegative control subjects. These results show that bystander activation occurs during primary HIV infection, even though HIV-specific CD8(+) T cells express the highest level of activation. The role of this bystander activation in lymphocyte homeostasis and HIV pathogenesis remains to be determined.