Genetically Engineered Poison That Targets HIV is Studied in Humans

"The intention, when we have determined the ideal dosing scheme, is that over time the drug
will reduce the body's burden of virus by selectively killing only the cells the virus has infected,"
says Dr. Davey. "We hope by reducing or eliminating the cellular reservoir of HIV, the pace of
progressive HIV-1 disease may be slowed or halted."
For the study, 24 HIV-infected individuals received single intravenous doses of either 1, 5,
10, 15 or 45 micrograms of drug per kilogram body weight.
"We found that the doses in two of three patients receiving 45 micrograms per kilogram of
sCD4-PE40 were not well tolerated," says Dr. Davey. "On the other hand, doses of 15 micrograms
per kilogram or lower caused much fewer side effects."
The investigators found that the major dose-dependent side effect was a temporary elevation
of liver enzymes that generally peaked 48 hours after the participants had received drug. Other minor
side effects included occasional fatigue, flushing, headache and mild fever.
Dr. Davey and his colleagues now are testing multiple doses of sCD4-PE40 for safety and
effects on the immune system using this same group of HIV-infected individuals.
Dr. Davey's coauthors include Christine M. Boenning, R.N.; Betsey R. Herpin, R.N.; Julia
A. Metcalf, B.S.; Robert E. Walker, M.D.; and H. Clifford Lane, M.D., from the Laboratory of
Immunoregulation of NIAID; Michael A. Polis, M.D., M.P.H; Judy Falloon, M.D.; Joseph A. Kovacs,
M.D.; M. Smolskis, R.N.; and Henry Masur, M.D., from the NIH Clinical Center; and D. H. Batts,
M.D., S. R. Cox, Ph.D., and L. Wathen, Ph.D., from The Upjohn Co.
NIAID, directed by Anthony S. Fauci, M.D., is one of 13 research centers of the National
Institutes of Health and investigates allergies, immunology and infectious diseases. In addition to
researchers working in NIAID laboratories in Bethesda, Md., and Hamilton, Mont., the Institute
supports scientists at U.S. universities, medical schools and research institutions.
The presentation, "A Phase I Study of Recombinant CD4-Pseudomonas Exotoxin (CD4-PE4O)
In HIV-Infected Individuals," is part of the Conference session "New Antiretrovirals: Non-Reverse
Transcriptase Inhibitors."