AIDS announcement raises questions.

AIDS announcement raises questions

A claim by French researchers that the immune-suppressive drug cyclosporine works well against AIDS, the ultimate manifestation of immune suppression, has met with widespread disapproval from the U.S. scientific community. But the criticism won't stop the drug's clinical trials, one of the French scientists told SCIENCE NEWS this week.

Jean-Marie Andrieu, who with Philippe Even and Alain Venet of Laennec Hospital in Paris held a press conference last week to announce "dramatic' improvement in two of six patients on cyclosporine for up to eight days. Andrieu declined to update the first week's results, saying they are reserving the details for the scientific community.

In a telephone interview, he said "it's going well' and that five other groups around the world have begun trials. Andrieu and his colleagues are pursuing the treatment with "many' new patients at Laennec, a public assistance hospital. It is not connected with the Pasteur Institute, the Paris research facility that first identified the AIDS virus. The Pasteur Institute is withholding judgment on cyclosporine, pending more data.

Several U.S. scientists expressed concern about the short period of time the patients had been treated. Improvement, they said, could have been due to one of the syndrome's periodic remissions. In addition, they criticized the lack of data given and the forum for the presentation.

Martin S. Hirsch of the Massachusetts General Hospital in Boston, who is investigating several AIDS drugs in clinical trials, comments, "At the moment we don't have any evidence cyclosporine has any effect in AIDS. It's extremely hard to fathom how in six days cyclosporine could have such a dramatic effect on the disease.'

Hirsch is worried that patients will get cyclosporine--which, unlike other AIDS drugs under investigation, is readily available by prescription--before its value is determined. "We're talking about a drug with a lot of potential risks,' he says. Among the risks: kidney toxicity and increased susceptibility to infection.

Responding to criticism from U.S. researchers, Andrieu says, "This is their own problem. Maybe they're right to criticize, maybe they're wrong.' His group announced the results in a press conference rather than at a scientific meeting or in a publication in order to get the word out quickly, he says.

If cyclosporine does work, it presents a paradox: How can an immune suppressor reverse a syndrome caused by a suppressed immune system? It does so by slowing or stopping interleukin-2, an immune system modulator, says Andrieu. Interleukin-2 inactivates the T4 cells, which are the cells infected by the AIDS virus. By "resting' these cells, Andrieu says, cyclosporine inhibits the viruses within them from replicating and spreading.

Allan Hess of Johns Hopkins University in Baltimore, who has studied the use of cyclosporine in organ transplants, hypothesizes that the drug could conceivably work by inhibiting the white blood cells that kill virally infected T4 cells. Other AIDS drugs currently under investigation work by inhibiting viral replication, but cyclosporine has not been shown to have this ability, says Hess.

Cyclosporine may share a limitation with other AIDS drugs under study--failure to cross the blood-brain barrier into the central nervous system. Recent studies have shown that the virus can infect brain cells (SN: u/12/85, p. 22); drugs that don't cross the barrier will miss some of the viruses. Cyclosporine, says Hess, is generally thought not to cross the blood-brain barrier.

The maker of cyclosporine, Sandoz, Ltd. of Basel, Switzerland, is planning to begin U.S. clinical studies after consultation with the Food and Drug Administration.