ACTIVATION OF LATENT VIRUS CONCURRENT WITH HAART IN AIDS

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DESCRIPTION: (Adapted from the investigator's abstract) The long term goal of this project is to greatly reduce on eliminate replication- competent virus from the latent pool of infected cells in HIV-1 infected subjects. Current anti-retroviral agents are highly effective in preventing viral replication in naïve cells but cannot eliminate latent virus from previously infected cells. The investigators will activate the virus by attempting to activate all the T cells, using an anti-CD3: anti-CD8 (CD3,8) bispecific monoclonal antibody (BSMAB) plus low dose IL-2. The cytokines released by the activated T cells is expected to activate the virus in infected non-T cells. Actively replicating virus will lyse the infected cells while new infection is prevented by highly active anti-retroviral therapy. Due to the unique properties of the CD3, 8 BSMAB that can lead to preferential outgrowth of the CD4+ T cells, they will also examine for evidence of expansion of the CD4+ T cells. AIM 1. Determine whether there is reduction/ elimination of latent HIV by pan-activation of T cells in the presence of HAART. In the presence of HAART, they will examine whether subjects treated by either of two low doses of CD3,8 plus IL-2 are able to significantly reduce the latent virus pool in comparison with subjects treated with low dose IL-2 alone. They will also examine the adverse effects induced by, and the tolerance of, this regimen by the subjects. The investigators will examine the kinetics of this reduction by examining for persistence of inducible virus by serial lymphoid tissue aspirate/biopsy and assay of PBMC. AIM 2. Determine whether there is an increase in the number of CD4+ T cells, enhancement of the immunologic function, and correction of immunologic imbalances. They will examine if the combination of CD3,8 and low dose IL-2 will induce CD4+ T cells, and to a lesser extent CD8+ T cells, functions in vivo. AIM 3. Determine the virologic and immunologic effect of three doses versus a single dose of CD3,8. They will determine whether there is any significant superiority in viral reduction and desired immunological changes, and whether there is increased toxicity. AIM 4. Provide information for optimizing the design of future experiments utilizing the similar strategies. Based on information obtained from this pilot study, they will seek to optimize future regimens regarding the optimal dose and duration of CD3,8, duration of concurrent IL-2 and composition and duration of HAART.