A CONTROLLED, PHASE-1 CLINICAL-TRIAL TO EVALUATE THE SAFETY AND EFFECTS IN HIV-1-INFECTED HUMANS OF AUTOLOGOUS LYMPHOCYTES TRANSDUCED WITH A RIBOZYME THAT CLEAVES HIV-1 RNA

This Phase I study, ''Ribozyme Gene Therapy of HIV-1 Infection'' (UCSD HSC #971072, FDA BB-IND 6405), is a prospective, open-label trial of infusion of autologous gene-altered cells into asymptomatic HIV-1 sero positive individuals. The objectives of this trial are to test the saf ety, feasibility, and potential efficacy of T-cell ribozyme gene thera py of HIV-I infection. To accomplish this, autologous CD8-depleted mon onuclear cells are transduced with ribozyme expressing or control muri ne retroviral vectors, expanded ex vivo, and and infused. Subjects are monitored intensively to determine effects of infusion on HIV burden and replication. Hn addition, in vivo survival of control and ribozyme transduced cells is followed in an effort to obtain evidence of proof of concept. A unique strategy of sample blinding is introduced in thi s protocol, wherein both subject and control specimens are supplied to the research laboratory as coded samples, spiking blood from HIV sero positive volunteers matched for CD4 lymphocyte count with known but va rying numbers of cells transduced with each vector. While this study i s still in progress, preliminary results indicate that infusion of gen e-altered, activated T-cells in HIV infected patients is safe, and tha t transduced cells can persist for long intervals in HIV-infected subj ects. Results also suggest ribozyme transduced cells may possess a sur vival advantage in vivo.