Usefulness of Therapeutic Drug Monitoring of Rilpivirine and relationship with virologic response and resistance in a cohort of naive and pre‐treated HIV‐infected patients

AIMS: The purpose of this study was to assess the antiviral activity of the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination and to describe the pharmacokinetics of rilpivirine and its association with resistance in clinical routine. METHODS: A retrospective multicenter cohort study was performed in both naive and pre-treated HIV patients receiving the once-daily rilpivirine/emtricitabine/tenofovir disoproxil fumarate regimen. Immuno-virologic and resistance data, and rilpivirine plasma trough concentrations were collected over the follow-up. Statistical analyses were performed to evaluate the relationship between RPV PK and virological response. ROC curve analysis was performed to determine the best target rilpivirine trough concentration. RESULTS: Overall 379 patients were included. After a median follow-up of 28 months, 26% of patients discontinued mainly due to toxicity and the virological success rate was 65.7%. Virological failure occurred in 5% of patients. A significant proportion of patients with HIV-RNA >40 copies/mL displayed rilpivirine plasma trough concentrations below the currently used 50 ng/mL efficacy threshold at both M6 (28%) and M12 (31%) in agreement with a significant lower median rilpivirine plasma trough concentration compared with patients virologically suppressed. Half of the patients with virologic failure who acquired rilpivirine resistance mutations had at least one suboptimal rilpivirine trough concentration. The optimal target for rilpivirine trough concentration found was 70 ng/mL (sensitivity 75.4%; specificity 61.5%). CONCLUSIONS: This study shows the impact of rilpivrine plasma trough concentration on both virological response and the emergence of rilpivirine mutations. Moreover, our results suggest that a higher target of rilpivirine trough concentration could be proposed in clinical practice.