Rilpivirine (RPV), a recently developed, once daily human immunodeficiency virus non-nucleoside reverse transcriptase inhibitor, is not currently approved for pediatric patients, but is sometimes prescribed for adolescents with multiple treatment failures, for regimen simplification or to minimize toxicity. Darunavir/ritonavir (DRV/r) administered once daily is also increasingly used in adolescents and may alter RPV pharmacokinetics (PK). We evaluated the PK interactions between RPV and DRV/r once daily in adolescents and young adults.
Human immunodeficiency virus–infected subjects 12 to <24 years old receiving a stable background therapy including RPV 25 mg once daily without or combined with DRV/r 800/100 mg once daily were enrolled. Intensive 24-hour blood sampling was performed, and PK indices were determined using noncompartmental analysis. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen.
Fifteen subjects receiving RPV without and 14 subjects with DRV/r were enrolled. When dosed without DRV/r, the RPV geometric mean (90% confidence interval) for RPV AUC0-24, Cmax and C24 h were 2.38 μg h/mL (1.92–2.94), 0.14 μg/mL (0.12–0.18) and 0.07 μg/mL (0.03–0.10), respectively, similar to adult values. RPV concentrations were significantly increased with concomitant DRV/r use: RPV AUC24, Cmax and C24 h were 6.74 μg h/mL (4.89–9.28), 0.39 μg/mL (0.27–0.57) and 0.23 μg/mL (0.17–0.32), respectively, well above the target ranges based on adult data. DRV/r PK was not affected by coadministration of RPV.
RPV PK in this adolescent population was similar to adults when dosed without DRV/r. DRV/r coadministration increased RPV exposure 2- to 3-fold, indicating that drug-related side effects should be closely monitored.
From the *Columbia University Medical Center, New York, NY; †Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; ‡Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY; §National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maternal and Pediatric Infectious Disease Branch, Bethesda, MD; ¶HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Contractor to NIAID, NIH, DHHS, Bethesda, MD; ‖Frontier Science & Technology, Amherst, NY; **Harvard School of Public Health, Boston, MA; ††Abbvie, Chicago, IL; ‡‡The University of Alabama at Birmingham, Birmingham, AL; and §§Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
Accepted for publication December 24, 2015.
This study was supported by National Institutes of Health (NIH), USA. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors have no conflicts of interest to disclose.
Address for correspondence: Marc Foca, MD, Columbia University Medical Center, New York, NY 10032. E-mail: firstname.lastname@example.org.