This project is directed at delineating the pathogenic mechanisms of human immunodeficiency virus (HIV) infection and the role of immune activation in the propagation of disease and destruction of the immune system. We studied the effect of immunization with a common recall antigen on viral expression in 13 HIV-1- infected patients by examining both the ability to isolate virus and changes in plasma viremia. In addition, the difference in susceptibility to HIV-1 infection of peripheral-blood mononuclear cells (PBMCs) from control subjects not infected with HIV-1 before and after tetanus immunization was examined. We demonstrated that, after tetanus toxoid booster inoculation, all 13 HIV-1-infected patients had transient increases in plasma viremia as well as increases in proviral burden (11/13) patients. Lymph node tissue in 2/2 patients examined also had increases in proviral burden and viral RNA after immunization as compared to lymphoid tissue obtained pre-immunization. HIV was more easily isolated from the PBMCs of the majority of patients after immunization than before immunization. Although all patients showed evidence of increased immune activation of PBMCs post immunization, there was no significant correlation between the magnitude of the increase in plasma viremia and magnitude of the specific immune response to tetanus as measured by tetanus-antibodies, in vitro tetanus-specific proliferation or increment of activation markers post immunization. However, there was a tendency for patients with higher CD4+ T-cell counts to show a greater fold increase in plasma viremia. PBMCs from HIV-seronegative individuals became more susceptible to in vitro infection with HIV after tetanus toxoid booster immunization. Preliminary studies demonstrated increased mRNA levels of TNF-alpha, IL-6, and IFN-gamma within PBMCs of HIV-infected and uninfected individuals post tetanus booster, further supporting a role role for proinflammatory cytokines in upregulating HIV expression in vivo.
