Impact of Protease Inhibitor-Based Antiretroviral Therapy on Tacrolimus Intrapatient Variability in HIV-Positive Kidney Transplant Recipients

Background. Human immunodeficiency virus (HIV)-positive kidney transplant (KT) recipients have been shown to experience higher rejection rates due in part to drug-drug interactions between antiretroviral therapy (ART) and immunosuppression regimens. High tacrolimus (FK) intrapatient variability (IPV) is associated with inferior outcomes in KT. The purpose of this study was to determine the impact of protease inhibitor (PI)-based ART on FK IPV and graft outcomes. Methods. We performed a single-center review of HIV-positive KT recipients from 2007 to 2017. Percentage coefficient of variation (%CV =(sigma/mu) x 100; sigma, median; m, standard deviation) was calculated for FK IPV. FK IPV at 6 and 12 months, graft function, and immune outcomes in PI-based vs non-PI-based KT recipients were compared. Results. A total of 23 HIV-positive KT patients were identified, of whom 10 were maintained on PI-based ART. Median IPV for the entire cohort at 6 and 12 months was 35.8% and 41%, respectively. Patients on PI-based regimens were proportionally more likely to experience high IPV at both time points. Median FK IPV was numerically higher at 6 months (37.3% vs 26.8%, P = .11) and significantly higher at 12 months (57.8% vs 30.9%, P = .01) for patients on PI-based regimens. Lastly, inferior graft function was observed in PI-based patients. Conclusion. Our data suggest that PI-based ART is associated with a higher degree of FK IPV, which may contribute to worsening graft function. Larger studies are warranted to determine the impact of PI-based ART on FK IPV and graft outcomes in this population.