Isabelle Poizot-Martin1, Caroline Solas, Julie Allemand, Véronique Obry-Roguet, Vincent Pradel, Sylvie Bregigeon, Olivia Faucher, Bruno Lacarelle. 1. *Aix-Marseille University, APHM Sainte-Marguerite, Service d'Immuno-Hématologie Clinique, INSERM U912 (SESSTIM), Marseille, France †Aix-Marseille University, APHM La Timone, Laboratoire de Pharmacocinétique et de Toxicologie, CRO2-INSERM, UMR911, Marseille, France ‡Département de Biostatistique et Informatique Médicale, Centre Hospitalo-Universitaire Sainte Marguerite, Marseille, France.
Abstract
OBJECTIVE: Tenofovir disoproxil fumarate (TDF) is known to induce renal dysfunction in HIV-infected patients. The aim of this retrospective study was to evaluate the correlation between TDF trough concentration (Ctrough-TDF) and glomerular filtration rate (GFR) in a cohort of patients on antiretroviral therapy. METHODS: A total of 163 patients with at least one determination of Ctrough-TDF between 17-24 hours were retrospectively selected from a computerized database and distributed into 3 groups defined by TDF concentrations <40 (11.7%), between 40 and 90 (36.8%), and >90 (high-level group, 51.5%) ng/mL. GFR was measured by Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration formulae at the times of TDF initiation and Ctrough-TDF determination and after 12 months. RESULTS: At the time of Ctrough-TDF measurement, median duration of TDF-based therapy was 21.1 months. GFR was significantly decreased in high-level group (-8.5 mL/min; P < 0.001) whatever the method used. GFR decline was significantly associated with an older age. Gender-stratified analysis showed that the early impact of Ctrough-TDF >90 ng/mL was significant in women only. After 12 months, the decrease in GFR in patients with high Ctrough-TDF was observed in both men and women (-8.27; P = 0.003). CONCLUSIONS: The high prevalence of elevated Ctrough-TDF and its correlation with an increased risk of renal impairment support the usefulness of therapeutic drug monitoring for TDF, particularly in women and older patients.
OBJECTIVE:Tenofovir disoproxil fumarate (TDF) is known to induce renal dysfunction in HIV-infectedpatients. The aim of this retrospective study was to evaluate the correlation between TDF trough concentration (Ctrough-TDF) and glomerular filtration rate (GFR) in a cohort of patients on antiretroviral therapy. METHODS: A total of 163 patients with at least one determination of Ctrough-TDF between 17-24 hours were retrospectively selected from a computerized database and distributed into 3 groups defined by TDF concentrations <40 (11.7%), between 40 and 90 (36.8%), and >90 (high-level group, 51.5%) ng/mL. GFR was measured by Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration formulae at the times of TDF initiation and Ctrough-TDF determination and after 12 months. RESULTS: At the time of Ctrough-TDF measurement, median duration of TDF-based therapy was 21.1 months. GFR was significantly decreased in high-level group (-8.5 mL/min; P < 0.001) whatever the method used. GFR decline was significantly associated with an older age. Gender-stratified analysis showed that the early impact of Ctrough-TDF >90 ng/mL was significant in women only. After 12 months, the decrease in GFR in patients with high Ctrough-TDF was observed in both men and women (-8.27; P = 0.003). CONCLUSIONS: The high prevalence of elevated Ctrough-TDF and its correlation with an increased risk of renal impairment support the usefulness of therapeutic drug monitoring for TDF, particularly in women and older patients.
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