Conclusions
No remarkable interactions between darunavir/ritonavir and raltegravir in plasma or cells were seen. Raltegravir IC concentrations are higher than previously reported; the difference being due to modified cell isolation procedures that reduced drug loss caused by washing.
Methods
HIV-infected patients on antiretroviral therapy received raltegravir 400 mg twice daily for 21 days (period 1); darunavir/ritonavir 800/100 mg once daily was added for 14 days (period 2), and patients were randomized to continue raltegravir twice daily (group 1) or to switch to 800 mg once daily (group 2), then they all stopped raltegravir intake and continued darunavir/ritonavir once daily for 14 days (period 3). Drug concentrations in plasma and cells (peripheral blood mononuclear cell) were measured, and differences in geometric mean ratios (GMR) and 90% confidence intervals (CI) between period 2 versus period 3 and period 2 versus period 1 were assessed.
Results
Twenty-four patients completed the study. Group 1 GMR (90% CI) of darunavir area under the curve (AUC) with and without raltegravir was 1.24 (1.13 to 1.45) for plasma and 1.24 (1.07 to 1.73) for cells and for group 2 was 1.14 (1.07 to 1.24) and 1.03 (0.94 to 1.16). GMR (90% CI) of raltegravir AUC without and with darunavir/ritonavir (plasma and cells) for group 1 was 0.90 (0.73 to 1.44) and 1.02 (0.81 to 1.67) and for group 2 was 1.21 (1.03 to 1.77) and 1.27 (1.07 to 1.94). Geometric mean IC to plasma AUC ratios were 5.3 and 4.9 for darunavir in groups 1 and 2 when darunavir/ritonavir was given alone and 4.9 and 5.6 for raltegravir when given alone. These ratios were not altered by the coadministered drug. Conclusions: No remarkable interactions between darunavir/ritonavir and raltegravir in plasma or cells were seen. Raltegravir IC concentrations are higher than previously reported; the difference being due to modified cell isolation procedures that reduced drug loss caused by washing.