Expression of a protective gene prolongs survival of T cells in human immunodeficiency virus-infected patients (gene therapy/Rev/transdominant/biolistics)

The resistance of acquired immunodefi- ciency syndrome (AIDS) to traditional drug therapy has prompted a search for alternative treatments for this disease. One potential approach is to provide genetic resistance to viral replication to prolong latency. This strategy requires the definition of effective antiviral genes that extend the survival of T cells in human immunodeficiency virus (HIV)-infected individuals. We report the results of a human study designed to determine whether a genetic intervention can prolong the survival of T cells in HIV-infected individuals. Gene transfer was performed in enriched CD4+ cells with plasmid expres- sion vectors encoding an inhibitory Rev protein, Rev M1O, or a deletion mutant control, ARev M1O, delivered by gold microparticles. Autologous cells separately transfected with each of the vectors were returned to each patient, and toxicity, gene expression, and survival of genetically modified cells were assessed. Cells that expressed Rev M1O were more resistant to HIV infection than those with ARev M1O in vitro. In HIV-infected subjects, Rev M1O-transduced cells showed preferential survival compared to ARev M1O controls. Rev