Background: The hallmark of HIV-1 infection is the decline of CD4+ T lymphocytes. We have suggested that autoimmune or autoimmune-like activity is involved in the destruction of CD4+ cells in HIV patients. The purpose of this study was to test this hypothesis in a novel therapeutic approach.
Design: In preliminary studies we found that T-cells isolated from seropositive patients are significantly more responsive to recombinant CD4 (rCD4) as compared to normal healthy seronegative donors. Moreover we isolated rCD4 T-cell lines from HIV seropositive patients which were able to kill autologous CD4+ cells. We therefore designed a T-cell vaccination protocol, using autologous anti-CD4 autoreactive T- cells as vaccines given to HIV-infected patients. The immune response induced by this vaccination is directed specifically against the autoreactive T-cells attacking the CD4+ cells. Ten million PHA-activated autologous cells were cultured in medium containing IL-2 and recombinant human CD4. Following such stimulation the cells were
tested for their response to rCD4 and cytotoxicity against autologous CD4. The cells that showed such reactivity were fixed with glutaraldehyde and administered subcutaneously in saline.
Results: Seven patients were injected: 2 received 3 injections at 2-month intervals, 3 received 2 injections, and 2 only 1 injection. No toxicity effect was observed in all patients injected. Significant increase in CD4 levels following vaccination with no significant change in HIV plasma viral load was observed in 4 patients, while in the other 3 no decrease of CD4 levels occurred.
Conclusions: Though this is only a phase 1 clinical trial, designed to evaluate safety and feasibility, it offers a novel approach for the treatment of HIV infection which will have to be tested in a larger number of patients. We are now emabarking on such a trial.
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