AEGiS-GMHC: Treatment Briefs: Rev-ing Up

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Treatment Briefs: Rev-ing Up

GMHC Treatment Issues, Vol. 10, No. 4 - April 1996

Another slowly advancing high-tech antiviral strategy is the "rev mutant" gene therapy investigated by Gary Nabel, M.D., of the University of Michigan. Some mutant versions of the rev protein hobble production of new HIV particles in cells by blocking the transport of necessary material from the nucleus. Dr. Nabel found that cells grown with HIV in the lab survived longer when the gene for this protein had been added to their normal gene set.

In the new study, CD4 cells were extracted from three HIV-infected people. Half of each person's cells were injected with the antiviral mutant gene and half with a neutral mutant gene. Gold microparticle "bullets" successfully implanted the genes in ten percent of the cells. Altered cells were treated with delavirdine to eliminate any HIV present and IL-2 to stimulate rapid proliferation. They were then reinfused into the source patient.

After the first infusion, only very small numbers of the cells could be detected. Patients no. 2 and no. 3 then received a second treatment utilizing ten billion, rather than one billion, cells. In patient 2, the half-life of the cells with the antiviral gene was four days versus one day for the control cells. In patient 3, the half-lives were around fifteen and 3.5 days for the anti-rev and control cells, respectively.

The slowed but relentless drop in the anti-rev cells may be due to instability of the transferred genes, or because even non-infected CD4 cells are subject to elimination in people with HIV. This issue may be resolved as Dr. Nabel's study continues, using different gene transfer methods to achieve a more stable integration of the protective gene in a higher proportion of cells.

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