ENHANCED T-CELL ENGRAFTMENT AFTER RETROVIRAL DELIVERY OF AN ANTIVIRALGENE IN HIV-INFECTED INDIVIDUALS

Intracellular expression of gene products that inhibit viral replicati on have the potential to complement current antiviral approaches to th e treatment of AIDS, We previously have shown that a mutant inhibitory form of an essential viral protein, Rev M10, prolongs the survival of T cells transduced with a nonviral vector in HIV-infected individuals , Because these gene-modified cells were not observed in patients beyo nd 8 weeks, efforts were made to improve the duration of engraftment, In this study, we used retroviral vector delivery of Rev M10 to CD4(+) cells and analyzed relevant immune responses in a pilot study of thre e HIV seropositive patients, DNA and RNA PCR analyses revealed that ce lls transduced with Rev M10 retroviral vectors survived and expressed the recombinant gene for significantly longer time periods than those transduced with a negative control vector in all three patients. Immun e responses were not detected either to Rev M10 or to Moloney murine l eukemia virus gp70 envelope protein, Rev M10-transduced cells were det ected for an average of 6 months after retroviral gene transfer compar ed with approximate to 3 weeks for the previously reported nonviral ve ctor delivery, These findings suggest that retroviral delivery of an a ntiviral gene may potentially contribute to immune reconstitution in A IDS and could provide a more effective vector to prolong survival of C D4(+) cells in HIV infection.