Usefulness of therapeutic drug monitoring of rilpivirine and its relationship with virologic response and resistance in a cohort of naive and pretreated HIV‐infected patients

• Published in: British journal of clinical pharmacology 2020-12, Vol.86 (12), p.2404-2413
• Main Authors: Néant, Nadège, Lê, Minh Patrick, Bouazza, Naïm, Gattacceca, Florence, Yazdanpanah, Yazdan, Dhiver, Catherine, Bregigeon, Sylvie, Mokhtari, Saadia, Peytavin, Gilles, Tamalet, Catherine, Descamps, Diane, Lacarelle, Bruno, Solas, Caroline
• Format: Article
• Language: English
• Subjects: antiretroviral therapy; HIV; Original; pharmacodynamics; pharmacokinetics; rilpivirine
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.14344

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 multicentre cohort study was performed in both naive and pretreated 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 rilpivirine pharmacokinetics and virological response. Receiver operating characteristic (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 was 70 ng/mL (sensitivity 75.4%; specificity 61.5%). Conclusions This study shows the impact of rilpivirine 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.