Nadège Néant1, Minh Patrick Lê2, Naïm Bouazza3,4,5, Florence Gattacceca6, Yazdan Yazdanpanah7, Catherine Dhiver8, Sylvie Bregigeon9, Saadia Mokhtari8, Gilles Peytavin2, Catherine Tamalet8, Diane Descamps10, Bruno Lacarelle1, Caroline Solas11. 1. Laboratoire de Pharmacocinétique et Toxicologie, Aix Marseille Univ, APHM, INSERM, CNRS, CRCM SMARTc, Hôpital La Timone, Marseille, F-13005, France. 2. APHP, Hôpital Bichat-Claude Bernard, Laboratoire de Pharmacologie-Toxicologie, IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité and INSERM, Paris, F-75018, France. 3. Université Paris Descartes, EA7323, Sorbonne Paris Cité, France. 4. Unité de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, France. 5. CIC-1419 Inserm, Cochin-Necker, Paris, France. 6. Aix Marseille Univ, INSERM, CNRS, CRCM SMARTc, Marseille, F-13005, France. 7. Univ Paris Diderot, APHP, IAME-UMR 1137, Hôpital Bichat-Claude Bernard, Service des Maladies Infectieuses et Tropicales, Paris, F-75018, France. 8. IHU Méditerranée Infection, Aix Marseille Univ., AP-HM, URMITE UM 63 CNRS 7278 IRD 198 INSERM 1095, Marseille, F-13005, France. 9. APHM, Hôpital Sainte-Marguerite, Service d'Immuno-hématologie clinique, Marseille, F-13009, France. 10. APHP, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité and INSERM, Paris, F-75018, France. 11. Aix Marseille Univ, APHM, INSERM 1207, IRD 190, UVE, Hôpital La Timone, Laboratoire de Pharmacocinétique et Toxicologie, Marseille, F-13005, France.
Abstract
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.
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 HIVpatients 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.
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