Once-daily treatment with saquinavir mesylate (2000 mg) and ritonavir (100 mg) together with a fixed-dose combination of abacavir/lamivudine (600/300 mg) or tenofovir/emtricitabine (245/200 mg) in HIV-1-infected patients

Objectives: To investigate the feasibility and pharmacokinetics of a once-daily regimen of 2000 mg saquinavir mesylate boosted with 100 mg ritonavir. Patients and methods: Patients successfully treated with 1000 mg saquinavir boosted with 100 mg ritonavir twice daily together with two nucleoside or nucleotide reverse transcriptase inhibitors [N(t)RTIs] who were switched to 2000 mg saquinavir with 100 mg ritonavir once daily with unchanged N(t)RTI therapy were analysed. CD4 cells, HIV-RNA PCR and metabolic parameters were compared between baseline and 3, 6, 9 and 12 months after the switch. Saquinavir and ritonavir drug levels were measured before and a median of 3 weeks after switching from twice to once daily at 0, 1, 2, 4, 6, 9, 12 and 24 h after intake of the medication. The area under the serum concentration-time curve from 0 to 24 h (AUC 0-24 ) was calculated using the trapezoidal rule. Results: Eighteen patients (16 males, median age of 41 years) with a median CD4 cell count of 464 cells/mm 3 were analysed. HIV-RNA PCR remained <500 copies/mL for all patients. After switching from 100 mg twice daily to 100 mg once daily, the AUC 0-24 for ritonavir decreased significantly [21874 to 10267 ng-h/mL, geometric mean ratio (GMR)=0.4 7 ; P<0.001], whereas the AUC 0-24 for saquinavir decreased only marginally from 35000 to 34490 ng·h/mL (GMR=0.99; P=0.426). The CD4 cell count and the fasting metabolic parameters remained unchanged. Conclusions: Once-daily treatment with ritonavir-boosted saquinavir was well tolerated and resulted in similar saquinavir drug exposure despite much lower ritonavir concentrations when compared with a twice-daily dosing schedule.