AIDSWEEKLY Plus, Monday, 24 February 1997
Daniel J. DeNoon, Senior Editor
A new protease inhibitor (PI) and a new nucleoside analog reverse transcriptase inhibitor (NARTI) packed a powerful anti-HIV combination punch in a clinical trial.
Glaxo Wellcome is developing both drugs.
The combination dropped viral load below the level of detection in most patients and increased CD4 counts. Two of the nine patients in the study withdrew after experiencing adverse events: nausea in one, and dysarthria and rash in the other.
The NARTI is 1592U89 succinate, called U89 by some and 1592 by others. It is a prodrug of the nucleoside analog carbovir; that is, it is activated to become carbovir after entering cells. Clinical trial subjects who have taken the drug alone or in combination with AZT have had significant viral load decreases and CD4 count increases. At the highest doses tested, nausea and headache were the most common adverse effects.
The PI is 141W94, formerly known as VX-478 and developed by Glaxo in partnership with Vertex Pharmaceuticals Inc. It is a peptidomimetic compound which, unlike most PIs, only weakly binds to human serum. Its pharmacokinetics are excellent: more than 70 percent oral bioavailability and a half-life of seven to ten hours.
University of Colorado researcher R.T. Schooley reported results from the 141W94/U89 study in a late-breaker session at the Fourth Conference on Retroviruses and Opportunistic Infections, held January 22-26, 1997, in Washington, D.C.
Nine adults who had never before received protease inhibitors received 141W94 at a dose of 900 mg b.i.d plus U89 at a dose of 300 mg b.i.d for four weeks.
For the seven patients for whom CD4 counts were available, median CD4 counts increased 79 cells/(micro)L from 223 cells/(micro)L at baseline.
For the six patients for whom viral load studies were available, viral load dropped by 1.97 log[10] from 41,700 RNA copies/mL. Viral load dropped below the level of detection in five of the six subjects.
"During the four-week evaluation period in this Phase I/II study, the combination of 141W94 and 1592U89 was generally well-tolerated and had significant antiviral activity," Schooley et al. wrote in their presentation abstract. "Further investigation of the combination is planned."
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