AIDSWEEKLY Plus, 8 July 1996
Daniel J. DeNoon, Senior Editor

Another of the new HIV protease inhibitors is being tested in a potent triple combination.

Nelfinavir mesylate (Agouron Pharmaceuticals Inc.) is the latest entry in what is now a field of four protease inhibitors being tested in combination with nucleoside-analog reverse-transcriptase inhibitors.

Early studies of nelfinavir in combination with stavudine (d4T) in patients with CD4 counts of at least 200 cells/(micro)L and HIV RNA levels of at least 15,000 copies/ml show that the drug decreases HIV RNA by 1.7 to 2.4 log[10] and increases CD4 counts by 105 to 133 cells/(micro)L after two months of treatment.

"I think this is an interesting combination for patients with late-stage disease," said Agouron researcher Dean Winslow.

Winslow presented his findings at the International Business Communications (IBC) workshop "HIV Protease Inhibitors," held June 11, 1996 in San Francisco, California.

Nelfinavir has a 95 percent effective dose of 40 ng/ml and a Ki of 2 nM. It has an oral bioavailability of 30 to 80 percent, which is enhanced by administration with food, and extensive tissue distribution.

Although the drug exhibits high protein binding, its low effective concentration permits administration in effective doses.

In an open-label, dose-ranging study nelfinavir monotherapy decreased HIV RNA levels by 1.5 to 2.4 log[10] and increased CD4 counts by up to 170 cells/(micro)L after four months of treatment. A dose of 750 mg tid is being used in ongoing trials; higher doses are associated with a 50 percent incidence of mild diarrhea.

Trials of nelfinavir in combination with AZT and 3TC are underway in the U.S. and Europe.

Preliminary results from these studies are expected to be released at the July 1996 XI International Conference on AIDS in Vancouver, Canada.

When tested in the same combination another protease inhibitor, indinavir (Merck), resulted in a sustained decrease of HIV RNA to undetectable levels in 90 percent of patients.

"Merck has set the benchmark for the triple combination," Winslow said.

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