The first protease inhibitor approved by the FDA, saquinavir is part of a new class of drugs for the treatment of advanced HIV infection. Saquinavir received approval for use in combination with older nucleoside analogue medications only three months after the FDA received the application for its marketing.

The FDA based its approval of saquinavir on clinical trials comparing three drug combinations in more than 900 HIV-infected individuals: saquinavir with AZT, saquinavir with ddC, and saquinavir with both AZT and ddC. The primary measure of drug effect was changes in patients’ CD4 cell counts, an indication of immune system strength. Values greater than 800 per milliliter of blood are normal in healthy individuals.

Over 16 weeks of treatment, CD4 cell counts increased an average of 30-40 cells per milliliter in subjects on saquinavir in combination with ddC, AZT or AZT plus ddC. Effects were attributable to combinations of saquinavir and a nucleoside analogue to which a subject had not been previously exposed. Saquinavir doses of less than 600 mg three times a day did not produce increases in CD4 cell counts. The duration of CD4 cell increases is not fully determined, although in general the increase lasted for at least the 16 weeks of the trials.

Saquinavir was granted as an accelerated approval, a regulatory mechanism under which the agency bases early approval for a product on laboratory markers such as CD4 cell counts, rather than on clinical endpoints such as delay in death or reduction in opportunistic infections.

Few adverse effects were associated with saquinavir; most patients tolerated the drug well.

Both protease inhibitors and nucleoside analogues chemically inhibit replication of the human immunodeficiency virus, although at different points in the replication process. Nucleoside analogues include the already-approved anti-HIV drugs AZT, ddC, ddI, d4T and 3TC.