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

Patients taking saquinavir will not be resistant to other protease inhibitors, clinical data suggests.

In vitro studies have shown that when HIV develops resistance to saquinavir (Invirase, Roche) it also becomes resistant to other protease inhibitors.

But clinical studies show a different situation in patients receiving the drug, according to Noel A. Roberts of Roche Products Ltd., U.K.

"Eighty-five percent of patients treated with saquinavir for one year remain sensitive to other protease inhibitors," Roberts said. "In more appropriate, more significant combinations we would expect saquinavir resistance incidence to decline even further."

Roberts made his remarks in a presentation to the International Business Communications (IBC) workshop "HIV Protease Inhibitors," held June 11, 1996 in San Francisco, California.

However, an expert in HIV resistance to protease inhibitors disagreed with Roberts's assessment of the data.

"The lack of saquinavir resistance in vivo, relative to that seen in vitro, could be due to the relative suboptimal activity of the compound," said Ronald Swanson of the University of North Carolina at Chapel Hill.

Researcher Emilio Emini of Merck Research Laboratories agreed with Swanson. Merck manufactures invirase (Crixivan), another protease inhibitor.

But Roberts noted that analysis of more than 1500 protease sequences from HIV isolated from patients at baseline and during saquinavir treatment (for up to three years) revealed a pattern of resistance distinct from that seen with other protease inhibitors.

In another study, virus isolates from 16 patients treated with saquinavir for at least six months were studied for sensitivity to three other protease inhibitors: Merck's indinavir, Abbott's ritonavir, and Glaxo-Wellcome's VX-478.

There was a greater than four-fold decrease in sensitivity to indinavir in 4 of 16 (25 percent) patients, to ritonavir in 4 of 16 (25 percent) patients, and to VX-478 in 1 of 11 (9 percent) patients.

"Virus isolates from five patients [31 percent] had no mutations and no significant changes in sensitivity to any of the drugs tested," Roberts said.

"Preliminary phenotypic studies indicate that virus carried by 80 to 90 percent of patients should remain sensitive to indinavir, ritonavir, or VX-478 after one year of saquinavir treatment."

Roberts also reported preliminary data from a small clinical trial of combination therapy with saquinavir, zidovudine (AZT), and lamivudine (3TC).

Study participants had a median HIV RNA level of 4.84 log[10] copies/ml and a median CD4 count of 336 cells/(micro)L at study entry.

Results after 16 weeks of treatment showed that 11 of 30 subjects (37 percent) had a reduction in HIV RNA below the limits of detection (200 copies/ml).

No serious adverse events were reported.

"Saquinavir is really a very safe drug," Roberts said.

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