A RANDOMIZED, PLACEBO-CONTROLLED, BLIND ANTI-AIDS CLINICAL-TRIAL - SAFETY AND IMMUNOGENICITY OF A SPECIFIC ANTI-IFN-ALPHA IMMUNIZATION

HIV-induced cytokine dysregulation, including overproduction of the an tiproliferative and cytolytic IFN alpha cytokine, represents a major c omponent of the immune disorders characterizing AIDS. To block the ove rproduction of IFN alpha we designed an AIDS vaccine combination which included both an anti-HIV and/or an anti-IFN alpha immunization. The safety and immunogenicity of this multicomponent vaccine were tested i n mice, Cercopithecus, two HIV noninfected individuals, and six HIV-1 seropositive immunocompromised patients enrolled in a 1-year open clin ical trial. We now report the result of a 9-month short-term randomize d, blind, placebo-controlled clinical trial (Phase I/II) performed in HIV-1 patients (22 individuals) to confirm safety/tolerance of the ant i-IFN alpha vaccine and its immunogenicity and to evaluate whether the complex vaccine initially used could be simplified by removal of HIV component(s). Three groups of patients received inactivated IFN alpha (i-IFN alpha) associated with the immunomodulator P40 with HIV-1 antig ens (groups B and C) or without (group A), and one group (D) was place bo. The clinical follow-up documented among those receiving i-IFN alph a showed that none developed AIDS and/or required antiretroviral chemo therapy. Viral load did not increase and CD4 cell count as well as cel l-mediated immunity (CMI) stabilized or even significantly increased i n group A. Immunogenicity of the preparations was determined by a posi tive delayed-type hypersensitivity (DTH) reaction to i-IFN alpha and t he presence of serum antibodies to i-IFN alpha and to HIV-1 peptides, occurring only in treated patients. As previously planned, based on th ese safety data, the trial has been extended for an additional year an d all patients were switched to protocol A (i-IFN alpha + P40). This s econd period of the trial, now open and ongoing, should allow us to ev aluate further the innocuity of the i-IFN alpha preparation and whethe r anti-IFN alpha vaccine could provide a longlasting CD4 cell count as well as CMI stabilization.