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Two AIDS drugs may be better than one.

Two AIDS drugs may be better than one

The drug zidovudine, also known as AZT, prolongs the lives of some AIDS victims and is the only drug federally approved for treating the disease. But it has its drawbacks. It does not cure AIDS, and often creates anemia, nausea and fatigue while decreasing levels of certain bone marrow cells. Rather than abandon zidovudine, researchers have begun investigating its use in combination with other drugs. They now report evidence that such combinations may work better to hinder the AIDS-causing virus, HIV. Says Samuel Broder of the National Cancer Institute (NCI), one of the first scientists to test zidovudine, "We make a great deal of progress in treating AIDS with already existing drugs."

Updating an ongoing clinical trial (SN: 2/6/88, p.84). the NCI's Robert Yarchoan reports that three patients receiving alternating one-week doses of zidovudine and a distantly related drug, 2'3'-dideoxycytidine (ddC), have passed the one-year mark with striking improvements in brain and peripheral nerve function and free of zidovudine's customary ill effects. Also promising is the finding, reported by the NCI's Carlo-Federico Perno, that drugs like zidovudine and ddC appear to halt HIV replication in macrophages, immune cells now recognized as one of the main targets of HIV infection. Previous research on AIDS drugs had focused mainly on immune cells called T-cell lymphocytes. Perno has discovered in vitro that zidovudine, ddC and other related drugs stop the spread of HIV in infected macrophages without harming the macrophages themselves. He noted this effect occurs with drug doses one-tenth to one-fifth the concentration used to obtain the same result in T-lymphocytes. Since macrophages carry HIV into the brain, the effect of zidovudine and ddC in cell culture may explain why they improve brain function in AIDS victims, says Perno, whose results will appear this month in the JOURNAL OF EXPERIMENTAL MEDICINE.

Together with zidovudine, another drug -- amphotericin methyl ester (AME)--also works better than either drug alone in combating

HIV in cell culture, reports Prem Sarin of the NCI. The two drugs may hit HIV with a double punch, says Sarin. While zidovudine inhibits the enzyme helping HIV reproduce, AME pokes holes in the protein coating surrounding HIV's genetic material. At yet another stage in the HIV cycle, Sarin has examined the drug abaerol, thought to block the packaging of HIV components into whole virus. Findings that will appear in an upcoming issue of BIOCHEMICAL PHARMACOLOGY show that abaerol also improves zidovudine's potency, he says. Therapies combining two drugs, such as AME or abaerol with zidovudine, are attractive because they allow doctors to lower dosages of each drug and thereby reduce the risk of side effects.

But other scientists advise caution in giving combinations of drugs. Mariano Busso of the Mount Sinai Medical Center in Miami reports certain drugs may diminish zidovudine's effectiveness. Busso and Lionel Resnick tested zidovudine given with each of three different molecular forms of the experimental AIDS drug dextran sulfate on two different laboratory isolates of HIV. One form of dextran sulfate increased zidovudine's potency in both isolates. But each of the two other varieties of dextran sulfate improved zidovudine's effectiveness in only one of the strains. In the other strain, each of the dextran sulfates counteracted zidovudine's anti-HIV action. These results suggest some patients may respond better than others to dextran sulfate, whose molecular formula and concentration are critical, Resnick says.

While experimental drug treatment in AIDS patients remains risky, scientists in the field agree it must continue. "Though there is toxicity with many drugs," Broder says, "scientists would be mistaken to wait for perfect solutions before conducting clinical trials on drugs against this lethal disease."
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Title Annotation:use of AZT in combination with ddc or AME
Author:Hendricks, Melissa
Publication:Science News
Date:Sep 10, 1988
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