A Review of Low-Dose Ritonavir in Protease Inhibitor Combination Therapy

Abstract

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.

Effectiveness of tipranavir versus darunavir as a salvage therapy in HIV-1 treatment-experienced patients

“…In our study, we did not observe an increase in either ALT or AST levels in the TPV-based regimen, as was observed in the RESIST trials; however, a significant increase in the baseline triglyceride levels through week 24 was observed within groups and after comparison between groups. This finding might be related to the higher dose of boosted ritonavir [13][14][15] detected in the TPV group (400 mg daily) compared with the lesser dose of boosted ritonavir in the DRV group (a higher dose led to an increase in triglycerides).…”

Drug-Drug Interactions as a Challenge in the Treatment of HIV/AIDS

“…Protease inhibitors have differing affinities for the CYP3A4 isoenzyme. The most potent inhibitor of CYP3A4 is ritonavir (Cooper et al, 2003), whereas the least potent is saquinavir. CYP3A4 inhibition associated with indinavir, nelfinavir, and amprenavir, and atazanavir tends to be intermediate.…”

HIV as a chronic disease

“…15 The resulting increased drug exposure improves virological and immunological outcomes. Unfortunately, the ritonavir boosting also results in gastrointestinal intolerance, dyslipidaemia, the accumulation of visceral fat and increased insulin resistance.…”