Correlation between the concentration of darunavir in PBMCs and plasma in the HIV-infected patients

Purpose: In the treatment of HIV-1 infection, proper maintenance of the concentration of darunavir (DRV) in blood is considered to be essential to prevent the proliferation of drug-resistant viruses, and therapeutic drug monitoring of DRV is considered to be an important tool to obtain the expected clinical efficacy as an alternative to counting CD4⁺cells or viral load. Recently, the importance for the measurement of the concentrations of DRV in PBMCs, the site of action for DRV, has been focused and discussed. In this study, we assessed the correlation between the concentration of DRV in human PBMCs and its level in plasma.

Methods: The whole blood was separated to PBMCs and plasma fractions using density gradient method. The concentration of DRV at trough was measured by HPLC-FLR method.

Results: We measured the concentration of DRV in four HIV-infected patients (3 male, 1 female). The mean concentration of DRV in PBMCs was 15.82 ng/10⁶ cells (12.35–19.19) and that in plasma was 4630 ng/mL (2610–5820). We found twice difference of ratio of DRV concentration in PBMCs to that in plasma among the patients All patients showed good response to anti-HIV therapy.

Conclusion: We found that PBMCs concentration was not predictable completely on the basis of the concentration of DRV in plasma, because PBMCs concentration vary largely in HIV infected patients. In this study, anti-HIV therapy with DRV for all patients showed good response. Some of the major weakness of sentinel site is small number of patients in this case. Further detail studies with larger volume of sample were required to clarify the impact of the concentration of DRV in PBMCs on the clinical effects.