NIAID Begins Study of New Drug for HIV Infection

SENT BY:NIAID/OFF, of COMMI

S 3-22-93;12:02PM; 301402012023

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H. Clifford Lane, M.D., NIAID clinical director, explains the rationale behind combining
different classes of drugs in HIV therapy: "Our current understanding suggests that the HIV
reverse transcriptase gene mutates at distinct sites In response to different drugs that Inhibit the
enzyme. For HIV to become resistant to two classes of drugs, it would have to develop mutations
at two sites. The chance of one virus developing both mutations and still being able to replicate is
quite small, and becomes even smaller when a thitd drug is added to the combination treatment."
"The use of combination therapy Is an established strategy In the treatment of infectious
diseases," he adds. "Drug combinations have been used for decades for diseases when the
development of resistance limits therapy, such as In the treatment of tuberculosis and many
cancers.
Previous and ongoing studies have demonstrated the promise of BHAP compounds in HIV
therapy. In the September 1992 Virology, Dr. Lane and colleagues at the Upjohn Company and
Georgetown University reported that BHAP compounds can sterilize HIV-infected cell cultures, the
first time this had been observed with a reverse transcriptase Inhibitor. Additional work on this
class of compounds has been carried out through the National Cooperative Drug Discovery Group,
NIAID-sponsored collaborations of government, university and private industry scientists.
Investigators at the NIH Clinical Center in Bethesda, ML, will enroll HlVdinfected patients
into the new study of U-90,152 In two phases, each of which will last 24 weeks.
For the Initial part of the study, participants must have 100 to 300 CD4+ T cells per cubic
millimeter (mm5) of blood, no serious signs or symptoms related to their HIV Infection, no history
of serious side effects to ddil or AZT and no previous treatment with non-nucleoside reverse
transcriptase inhibitors. CD4+ T cells are the crucial Immune cefls depleted during HIV infection.
A healthy. uninfected person usually has 800 to 1,200 CD4+ T cells/mm3.

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