title: Renal impairment in patients receiving a tenofovir-cART regimen: impact of tenofovir trough concentration.
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.
authors.affiliation: *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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poizot-Martin
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
authors.forename: Julie
authors.initials: J
authors.lastname: Allemand
authors.forename: Véronique
authors.initials: V
authors.lastname: Obry-Roguet
authors.forename: Vincent
authors.initials: V
authors.lastname: Pradel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bregigeon
authors.forename: Olivia
authors.initials: O
authors.lastname: Faucher
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012432:Rwanda; D000068698:Tenofovir
chemical_list: D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine