Assessment of Maraviroc Exposure–Response Relationship at 48 Weeks in Treatment‐Experienced HIV‐1–Infected Patients in the MOTIVATE Studies. (14th August 2013)

• Record Type: Journal Article
• Authors: Jacqmin, P; Wade, JR; Weatherley, B; Snoeck, E; Marshall, S; McFadyen, L
• Is Part Of: CPT: pharmacometrics & systems pharmacology. Volume 2:Number 8(2013:Aug.)
• Page Start: 1
• Page End: 9
• Publication Date: 2013-08-14
• Subjects: Pharmacokinetics -- Periodicals; Pharmacology -- Periodicals; Pharmacokinetics; Periodicals; 615.05
• DOI: 10.1038/psp.2013.42
• Languages: English
• ISSNs: 2163-8306

Abstract

Abstract : Efficacy exposure–response relationships of the CCR5 antagonist maraviroc were evaluated across two phase III clinical trials. This post‐hoc analysis used 48‐week efficacy data from 841 treatment‐experienced patients infected with CCR5‐tropic human immunodeficiency virus type 1 (HIV‐1), identified by the enhanced sensitivity Trofile assay. Probability of treatment success (viral RNA <50 copies/ml) was modeled using generalized additive logistic regression, testing exposure, clinical, and virologic variables. Prognostic factors for treatment success (in decreasing order of Akaike information criterion (AIC) change) were: maraviroc treatment, high‐weighted overall susceptibility to background treatment, absence of an undetectable maraviroc concentration, high baseline CD4 count (BCD4), low viral load (VL), race (other than black), absence of non‐R5 baseline tropism (BTRP), and absence of fosamprenavir (FPV). No concentration–response relationship was found with treatment (maraviroc vs. placebo) and presence/absence of undetectable maraviroc concentration (adherence marker) in the model. The maraviroc doses studied (300 or 150 mg with potent CYP3A4 inhibitors once (q.d.)/twice daily (b.i.d.)) deliver concentrations near the top of the concentration–response curve. CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e64; doi:10.1038/psp.2013.42 ; published online 14 August 2013