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The pharmacokinetics of protease inhibitors center around the microsomal enzyme cytochrome P-450 3A4. As a potent inhibitor of this enzyme, ritonavir can increase the bioavailability and half-life of coadministered protease inhibitors. Evidence suggests that increased exposure to protease inhibitors is clinically relevant. Antiretroviral treatment with low-dose ritonavir-boosted lopinavir, indinavir, and saquinavir has durable virological activity and shows impressive immune reconstitution. Although tolerable in most cases, gastrointestinal side effects, hepatotoxicity, and blood lipid abnormalities remain relevant issues. Additional study will elucidate the advantages and disadvantages of twice-daily, low-dose ritonavir-boosted regimens and determine whether once-daily regimens based on this principle will have a lasting role in clinical practice.