Etravirine Plasma Exposure is Associated with Virological Efficacy in Treatment-experienced HIV-positive Patients

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 <50 copies/mL) during follow up. Fifty-nine (84.7% male) patients were included: baseline CD4+ T-lymphocyte and HIV RNA were 276 cells/uL (101-419) and 3.99 Log10 copies/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 426 ng/mL (266-763) and 408 ng/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 >300 ng/mL (p=0.02) and etravirine wgIQ >276 ng/mL/mutation (p=0.02) were associated with virological success; at multivariate Cox proportional analysis etravirine wgIQ <276 ng/mL/mutation (p=0.012) and baseline CD4 <200 cell/uL (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 (300 ng/mL and 276 ng/mL) were proposed for etravirine Ctrough and wgIQ and need to be confirmed in prospective studies.