New Trial Recruiting at NIH: CD4-PE40

The first study of a new compound, called CD4-PE40, is currently seeking volunteers with T-helper counts of 500 or less. They must be willing to abstain from all other experimental therapies for four weeks prior to the trial and during the course of the four-week study; they may, however, take AZT if they wish. This is a dose escalation study looking primarily at how the new drug behaves in the body (pharmacokinetics) and at safety/toxicity. It requires at least three days of hospitalization and three subsequent outpatient visits at the National Institutes of Health (NIH) in Bethesda, Maryland, near Washington, D. C. This is not a long-term treatment trial; there are not expected to be any medical benefits for study participants. For more information, call Chris Boenning, R. N., M. S. N., at 800/772-5464, ext. 410, or Betsy Herpin, R. N., M. S. N., at ext. 304.

Note: Earlier clinical trials of soluble CD4 (and of CD4- IgG, the CD4 molecule with an IgG antibody attached to it to keep the compound in the bloodstream longer) have been disappointing, demonstrating no substantial signs of effectiveness in spite of dramatic anti-HIV results in test-tube studies. While most of the human trials of these compounds in adults are being abandoned, researchers at The Upjohn Company and the National Institutes of Health hope that by attaching pseudomonas exotoxin (PE40, a truncated form of a poison produced by the bacteria pseudomonas) to the CD4 molecule, they may achieve significant antiviral activity in people, as well as in laboratory studies.

Richard Davey, M. D., the principal investigator for this study, explained that part of the problem with previous CD4 molecules may have been that not enough of the drug was able to bind to HIV in the bloodstream to prevent the virus from infecting cells. It is hoped that the new compound will only need to bind to a few receptors on an HIV-infected cell in order to kill that cell. Dr. Davey believes that if this compound is helpful, it will probably need to be used in combination with antiretrovirals such as AZT, ddC, ddI, or one of the newer agents now being developed. The reason is that when HIV-infected cells are killed, virus may be released into the bloodstream, and antiviral drugs may then be needed to prevent the freed virus from replicating further.

The idea of combining CD4 with pseudomonas exotoxin is not new; a report that the combined protein selectively killed HIV- infected cells was published in Nature, September 22, 1988. The trial announced above is the first human test of this potential drug.