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Four new AIDS drugs show early promise

Findings reported at an L.A. conference signal possible fresh modes of attack against resistant strains of HIV.

March 01, 2007|Jia-Rui Chong | Times Staff Writer

Two experimental AIDS drugs designed to fight resistant HIV strains are showing promising preliminary results, researchers said Wednesday.

One, called elvitegravir, is part of a new class of drugs known as integrase inhibitors and has shown evidence of being more potent than currently used drugs.

The second, called TMC278, is a variation of an existing class of drugs known as reverse transcriptase inhibitors, but shows fewer side effects and appears to work against some resistant strains of HIV, researchers reported at the Conference on Retroviruses and Opportunistic Infections at the Los Angeles Convention Center.

The preliminary findings on the two drugs followed presentations Tuesday about two other HIV drugs that are closer to receiving federal approval -- raltegravir, an integrase inhibitor from Merck & Co., and maraviroc, a drug from Pfizer Inc. known as a CCR5 inhibitor. Both drugs were hailed as potentially among the biggest developments in HIV therapy since the mid-1990s.

Together, the presentations on all four drugs seemed to herald a long-awaited blossoming in new ways to treat the estimated 15% to 20% of patients who face full-blown AIDS because their viruses have grown resistant to other drugs.

Dr. Daniel Kuritzkes, director of AIDS research at Brigham and Women's Hospital in Boston who was not involved in any of the research, said he was excited by the possibility of so many new drugs that could attack the virus with a variety of methods. More methods mean less chance for the virus to mutate into a resistant strain, he said.

"We have every expectation we can suppress the virus in the vast majority of patients," Kuritzkes said.

Elvitegravir, developed by Foster City, Calif.-based Gilead Sciences Inc., works like other integrase inhibitors by blocking one of three enzymes crucial to HIV for replication inside human cells.

Because the drugs use a different strategy than other drugs, doctors hope they will be effective in patients whose virus has become resistant to the 20-odd approved drugs.

Dr. Andrew Zolopa of Stanford University studied 278 patients who were already receiving standard HIV drugs. In addition to those drugs, one group received a 50-milligram dose of elvitegravir, one received a 125-milligram dose and a third received a protease inhibitor.

Those receiving the 50-milligram dose got some benefit from the drug, but those receiving the higher dose had a 98% reduction of HIV in their blood after 24 weeks, compared with a 94% reduction in those receiving the protease inhibitor cocktail, according to the Gilead-funded study.

While elvitegravir appeared effective, Zolopa said he was concerned that viral levels tended to rebound slightly after a few weeks.

Testing will continue on elvitegravir, which Gilead officials said is unlikely to be available before 2009.

TMC278, which is being developed by Tibotec Inc. of Yardley, Pa., was specifically designed to breathe new life into reverse transcriptase inhibitors, which were the first family of AIDS drugs to be used.

They have been a mainstay of therapy, but there are many HIV strains that are resistant to the drugs.

Dr. Anton Pozniak of Chelsea and Westminster Hospital in London reported on a study of 368 patients who had not previously received HIV drugs. He said the new drug was about as effective in controlling the virus after 48 weeks as one of the most effective reverse transcriptase inhibitors, efavirenz.

The Tibotec-funded study showed that patients taking the drug were about half as likely as those taking efavirenz to suffer symptoms like daytime dreams, dizziness, nausea, sleepiness and rashes.


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