Authors:

Accardo

Department of Medical Sciences, University of Torino, Italy

Abstract:

Background: The NNRTIs currently used most frequently in clinical settings, in dual and triple medication regimens (2DR and 3DR), are doravirine (DOR) and rilpivirine (RPV). These medicines’ intracellular (IC) pharmacokinetics (PK) are not yet well understood. Comparing plasma PK and IC buildup in patients with real-world experience was our goal (pts). Methods: Consideration was given to patients on a DORand RPV-including antiretroviral (ARV) regimen. Using UHPLC-MSMS validated techniques, the plasma and IC (PBMCs) concentrations of DOR and RPV were assessed 12 hours (T12) and 24 4 hours (T24) after the last dose. Results: 90 points were included (65% on 3DR and 35% on 2DR): 48% of ARVs contained RPV, and 52% had DOR. The RPV IC/ plasma ratio was 6.034, which was much greater than the DOR IC/plasma ratio (4.878-7.186)Independent of timing T12 (p=0.003) and T24 (p0.00), the difference was 1.479 (1.256- 1.702) (p=0.001). In comparison to 2DR, RPV in 3DR led to greater buildup of plasma and IC. DOR and RPV plasma and IC concentrations were shown to be linearly and significantly correlated (+0.749, p0.001 and +0.733, p0.001). No statistically significant relationship between the overall DOR and RPV PK and creatinine, BMI, age, or gender differences was discovered. Conclusion: RPV demonstrated more accumulation in PBMCs than DOR: RPV and DOR IC levels were 498% and 50% higher than in plasma.

Citation:

Accardo. Doravirine and Rilpivirine Intra Cellular Accumulation in the Clinical Setting.. Clinical Imaging and Case Reports 2023.