Research published today shows that combination treatmentsfor AIDS may sidestep the problem of drug resistance causedby genetic mutations of HIV.
Mutations have enabled the virus to resist the nucleoside drugsAZT, ddI and ddC. The new findings suggest that the threecorporate giants developing these AIDS drugs -- BurroughsWellcome Co., Bristol Myers Squibb Co. and Hoffmann La RocheInc. -- could end up with their products cooperating to fightthe epidemic.
Resistant strains of HIV have emerged that no longer respondto the effects of AZT, the one nucleoside currently approvedfor use against AIDS. And ddI has come up against the sametherapeutic roadblock even before achieving market approval.
Researchers at Burroughs Wellcome, the maker of AZT, reporttoday in Science that resistance to ddI emerged in viralisolates from five patients who were switched to that drugwhen they began to deteriorate clinically after at least 12months on AZT. Cross-resistance to ddC was also observed inthese isolates.
However, the mutation that appeared with ddI resistanceseemed to "markedly diminish" the effect of a mutation thatconfers resistance to AZT, the scientists reported.
"Because the mutational basis of decreased viral sensitivity isdifferent for AZT and ddI, our findings give further support forthe use of multidrug therapy to treat HIV disease," theresearchers concluded. "Moreover, combinations of nucleosideanalogs ... might be sufficient to prevent resistant variantsfrom appearing."
Hoffmann La Roche is developing ddC and Bristol Myers isdeveloping ddI.
A letter from Australian researchers, to be published Saturdayin The Lancet, documents AZT resistance in 90 percent of 135patients who received the drug.
Viral isolates from five of the patients at Fairfield Hospital inVictoria who were taken off AZT -- usually because of theanemia side effect of the drug -- were seen to progressivelyregain sensitivity to AZT after the drug was withdrawn.
But isolates from the remaining 10 patients, who had takenAZT for an average of 23 months compared with seven to 18months for the other five patients, remained resistant up tosix months after the drug was stopped.
The report in Science also mentioned a selective polymerasechain reaction (PCR) procedure to detect the mutationassociated with ddI resistance. The method could be used tomonitor people switched from AZT to ddI for the appearance ofthe mutation, according to the Wellcome scientists.
-- Roberta Friedman, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.