Protease Inhibitors in Human Testing: Annotated List

This brief directory of some protease inhibitors includes company, generic name, brand name if known (in parentheses), and comments. It is included to help readers follow our coverage of these drugs.

* Merck & Co.: indinavir (Crixivan(R)). This drug appears to be generally the best regarded among treatment activists at this time. It has very good viral suppression, and apparently limited side effects. The main disadvantage is that viral resistance and cross resistance can develop rapidly, especially if the drug is used improperly. It is possible that indinavir might still provide some benefit against resistant viruses.

* Abbott Laboratories: ritonavir. The main advantage of ritonavir is that now it has proven survival benefit in advanced AIDS; the other protease inhibitors have not yet been tested in any trial that could have determined whether or not they also can keep people alive longer. Ritonavir's main disadvantage is serious interactions with a number of other drugs. Also there are often gastrointestinal side effects, at least with the current formulation.

* Hoffmann La-Roche: saquinavir (Invirase(TM)). This is the only protease inhibitor which is FDA-approved at this time. It seems to have less viral resistance problem than the Merck and Abbott drugs. Its main disadvantage is that it was approved at a dose which is clearly too low; drawbacks to just taking more include the drug's great expense, and the lack of much safety data at higher doses. The dosage problem is being corrected, with a new formulation which will deliver a higher dose economically; however, it will take some time to get enough clinical-trial experience with the new dose and formulation for the FDA to be confident of safety, and approve this formulation for marketing.

* Agouron Pharmaceuticals, Inc.: nelfinavir mesylate (VIRACEPT(TM)). See the clinical trials announcement, below.

* Glaxo Wellcome/Vertex: 141W94, or VX478. No information about this protease inhibitor was presented at the Retroviruses conference, except for a passing reference in one abstract.

* CIBA-Geigy Ltd.: CGP 61755. This drug is in early development, and is not yet available in trials in the U.S. There was one abstract at the conference.

* Pharmacia & Upjohn: This company's protease inhibitor has not yet been tested in people; the first small, single-dose human studies might start later this year. There was no information about this drug at the conference.