WASHINGTON _ Scientists long stymied by the maddeninglyresilient AIDS virus have begun exploring novel approaches toAIDS prevention and treatment _ including an attempt at genetherapy in three infected volunteers.

Gary Nabel, of the University of Michigan's Howard HughesMedical Institute in Ann Arbor, said his team has inserted boguscopies of HIV-1 genes into volunteers' blood cells, which were thenre-infused into their owners.

Ultimately, the researchers hope that flooding susceptible cells without-of-sequence HIV-I genes will hamper the virus's ability toreplicate and cause AIDS.

Nothing else, not even the highly touted AZT, used alone or incombination with other drugs, has halted viral reproduction for verylong. Not surprisingly, scientists conditioned by a decade of repeatedfailures are reluctant to predict that the new approach will fare anybetter than the others.

"There are so many ways that this virus can defeat us," Nabel saidhere Tuesday at the Second National Conference on HumanRetroviruses and Related Infections.

Harold Jaffe, director of HIV/AIDS for the Centers for DiseaseControl and Prevention in Atlanta, echoed the views of others at themeeting, saying he was reluctant to characterize the potential of theapproach because he knew too little about it.

Anthony Fauci, director of the National Institute of Allergy andInfectious Diseases, in Bethesda, Md., said the theory soundspromising, but scientists will have to determine whether thetechnique will work in large numbers of people.

Nabel said his team initially plans to try the approach on a dozenpatients. He hopes to have results within six months.

In essence, the method attempts to capitalize on HIV's tactic ofinfiltrating helper T cells and forcing the cells' genetic machinery tomake new copies of the virus. One of the viruses genes, called rev,helps assembled the newly created viral genes so they can infiltratemore viruses.

Nabel produces large quantities of mutant rev genes, whose sequenceis scrambled just enough to confuse HIV's reproductive machinery,which recognizes the gene, but cannot read the new sequence. Viralreplication stops.

One key challenge was figuring out a way to get the new genes intothe blood cells. Nabel's group solved that problem by coating tinygold particles with thousands of copies of the gene and then, using agas-powered gun, shooting them into the volunteers' blood cells. Theblood cells, which remain unharmed, are then injected into thepatients.

So far, Nabel said, the procedure seems safe. "The challenge is to seewhether this will work," he said.

Live Virus Vaccine Carries Seeds Of Destruction

In another novel genetic attempt to combat AIDS, scientists havecreated a live-virus AIDS vaccine that carries the seeds of its owndestruction _ a herpes gene that renders the attenuated circulatingvirus susceptible to the anti-herpes drug ganciclovir.

Scientists regard vaccines made from live but weakened viruses asmore likely to be effective against AIDS, because live viruses canprovoke a powerful immune response. But they fret that even aweakened form of HIV may cause fatal immune deficiencies, just aspeople have gotten polio from live attenuated polio vaccines.

So researchers at the National Institute of Allergy and InfectiousDisease decided to guarantee the safety of a live AIDS vaccine usinga "suicide gene," said Stephen Smith, who described the researchyesterday.

Because of the gene, he said, the HIV cells in the vaccine can bedestroyed once they provoke an immune response.

Other researchers cautioned, however, that the technique is a longway from clinical application _ if it works at all. The AIDS viruscan mutate so rapidly that it can theoretically expel the alien geneand go on to cause disease.

Chiron's Implant Delays CMV Retinitis

Chiron Vision (a unit of Chiron Corp.) reported Phase III results ofits intraocular ganciclovir implant showing it improved onintravenous ganciclovir in delaying progression of cytomegalovirus(CMV) retinitis.

Given the superior results, Chiron expects to file for market approvaleither late this quarter or in the second quarter, Larry Kurtz, Chiron'svice president of corporate communications, told BioWorld.

The implant contains ganciclovir embedded in a polymer-basedsystem that allows for sustained-release delivery. It is placed into theposterior part of the eye through a small incision, and can beremoved and replaced when depleted of the drug.

An investigator reported interim trial data on 148 patients. Resultsshowed that median time to progression of CMV retinitis was 186days for those using the implant vs. 72 days for eyes receivingintravenous ganciclovir, an approved therapy. Kurtz said thecompany is analyzing data from the remaining 40 patients, but"given the statistical significance, we don't expect the remaininganalysis will show any real different results."

Chiron, of Emeryville, Calif., licensed the implant from ControlDelivery Systems Inc., a Stamford, Conn., company founded by theproduct's inventors. Chiron will pay a royalty on sales.

In Other Conference News

* Gilead Sciences Inc., of Foster City, Calif., said a 48-patient PhaseII/III pivotal trial of Vistide in AIDS patients with CMV retinitisshowed statistical significance in delaying progression of the disease.

Patients received either immediate treatment with Vistide or deferredtreatment. Median time to progression was 120 in the immediate-treatment group vs. 22 days in the deferred treatment group. n

Jim Shrine contributed to this report.

-- Steve Sternberg Special To BioWorld Today

(c) 1997 American Health Consultants. All rights reserved.

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