The Food and Drug Administration approved the first three protease inhibitors, members of a new class of antiretrovirals that may be considered the most potent therapeutic agents for HIV to date. In order for these drugs to be effective, and to minimize the risk of resistance, it is important that these drugs are prescribed and taken in accordance with the products' approved labeling. These drugs have shown improvements in surrogate markers (increased CD4 and decreased viral load levels), leading to accelerated approval. In addition, clinical benefit has been shown with Norvir, which demonstrated a reduction in both mortality and AIDS-defining clinical events over 6 months, in studies of patients with advanced HIV disease.
Under dosing, noncompliance, or partial-compliance with dosing regimens for these drugs may result in development of a resistant strain(s) of HIV that will not be susceptible to treatment with protease inhibitors. Patients must be aware of the need to take the complete dose to lessen the risk of potential drug resistance. Patients should not modify the dosage in any way to "extend" their prescription.
The protease inhibitors are partially metabolized by the cytochrome P450 oxidase system and have a potential for serious interactions with a large number of commonly prescribed drug products metabolized by the same pathway.
The following tables profile the similarities and differences of each approved protease inhibitor, and provide useful information about dosing storage, potential drug interactions, and therapeutic options.