title: Etravirine plasma exposure is associated with virological efficacy in treatment-experienced HIV-positive patients.
abstract: Etravirine is a non-nucleoside reverse transcriptase inhibitor used in combination with other antiretrovirals for the treatment of HIV infection. Given previous conflicting results aim of this study was to investigate whether etravirine plasma exposure was associated with virological outcome. Adult HIV-positive patients starting etravirine with detectable HIV viral loads were included if highly adherent (<90% of the doses) and if steady-state plasma concentrations were available (measured through a validated HPLC-PDA method). Virological success was defined as reaching and maintaining viral suppression (HIV RNA <50copies/mL) during follow up. Fifty-nine (84.7% male) patients were included: baseline CD4+ T-lymphocyte and HIV RNA were 276cells/μL (101-419) and 3.99Log10copies/mL (3.11-4.91), respectively. Darunavir/ritonavir (n=21, 35.6%) and raltegravir plus maraviroc (n=33, 55.9%) were the most common associated antiretrovirals. 240 trough samples were available (3-7 per patient); etravirine trough concentrations (Ctrough) and weighted genotypic inhibitory quotients (wgIQ) were 426ng/mL (266-763) and 408ng/mL/mutation (227-663), respectively. Virological success was observed in 49 patients (83.1%). Genotypic sensitivity of associated drugs (GSS) ⩾2 (p=0.03), etravirine Ctrough >300ng/mL (p=0.02) and etravirine wgIQ >276ng/mL/mutation (p=0.02) were associated with virological success; at multivariate Cox proportional analysis etravirine wgIQ <276ng/mL/mutation (p=0.012) and baseline CD4 <200cell/μL (p=0.043) were independently associated with virological failure. In a cohort of experienced patients etravirine exposure as well as immune status were associated with virological success; two cut off values (300ng/mL and 276ng/mL) were proposed for etravirine Ctrough and wgIQ and need to be confirmed in prospective studies.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy. Electronic address: andrea.calcagno@unito.it.
authors.forename: A
authors.initials: A
authors.lastname: Calcagno
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Marinaro
authors.affiliation: San Raffaele Scientific Institute Milano, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Nozza
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Aldieri
authors.affiliation: San Raffaele Scientific Institute Milano, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.affiliation: Laboratory of Microbiology and Molecular Biology, Ospedale Amedeo di Savoia, ASLTO2, Torino, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Ghisetti
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Trentalange
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Avolio
authors.affiliation: San Raffaele Scientific Institute Milano, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Castagna
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bonora
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D006678:HIV / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010949:Plasma / Q000737:chemistry*; D011724:Pyridazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine
keywords: Etravirine; Experienced patients; Inhibitory quotient; Pharmacokinetics; Resistance