Our group has carried out bi-directional technology transfer between clinical and basic AIDS research in HIV in pioneering the first ACTG trial (ACTG 244) which uses drug/virus response driven therapy. This has been accomplished, in part, through the development of a monitoring system based on quantitative RNA PCR that allows rapid assessment of the pivotal pol gene mutations involved in ZDV resistance. This sort of response driven therapy has emerged as a new option in the development of HIV therapeutics, given the ability of the virus to produce variants, including drug escape mutants. We propose to incorporate this approach in an effort to evaluate HIV antigen specific cellular immunotherapies in man. Clinical virologists and immunologists together with cell biologists at Stanford University have combined with a cell therapy company, recombinant vaccine and cytokine manufacturers and a gene therapy developer at Duke University to prepare and administer, in vivo, antigen presenting cells as well as HIV specific cytolytic T cells. This collaboration should bring to HIV infected patients the products of biotechnology firms as well as those of our academic institution. Our extensive experience, beginning almost two decades ago, in defining and optimizing ways of utilizing human interferon in man should facilitate our proposed academic-industrial collaboration, with clinical results available within the tenure of the proposed grant. Pilot clinical trials will be monitored with new methods and conducted with new modalities supported by the grant. The latter will also support the background pathogenetic and disease monitoring required for achieving the goals of the project. Subsequent large scale clinical trials will require industrial or ACTG support, which is already in place for the first phase of the proposed studies.
