Abstract

ObjectivesThe study aimed to survey maraviroc use and assess effectiveness and durability of maraviroc-containing antiretroviral treatment (ART) in routine practice across Europe.MethodsData were retrieved from 26 cohorts in 8 countries comprising adults who started maraviroc in 2005–2016 and had ≥1 follow-up visit. Available V3 sequences were re-analysed centrally for tropism determination by geno2pheno[coreceptor]. Treatment failure (TF) was defined as either virological failure (viral load >50 copies/mL) or maraviroc discontinuation for any reason over 48 weeks. Predictors of TF were explored by logistic regression analysis. Time to maraviroc discontinuation was estimated by Kaplan-Meier survival analysis.ResultsAt maraviroc initiation (baseline), among 1,381 patients, 67.1% had experienced ≥3 ART classes and 45.6% had a viral load <50 copies/mL. Maraviroc was occasionally added to the existing regimen as a single agent (7.3%) but it was more commonly introduced alongside other new agents, and was often (70.4%) used with protease inhibitors. Accompanying drugs comprised 1 (40.2%), 2 (48.6%) or ≥3 (11.2%) ART classes. Among 1,273 patients with available tropism data, 17.6% showed non-R5 virus. Non-standard maraviroc use also comprised reported once daily dosing (20.0%) and a total daily dose of 150mg (12.1%). Over 48 weeks, 41.4% of patients met the definition of TF, although the 1-year estimated retention on maraviroc was 82.1% (95% confidence interval 79.9–84.2). Among 1,010 subjects on maraviroc at week 48, the viral load was >50 copies/mL in 19.9% and >200 copies/mL in 10.7%. Independent predictors of TF comprised a low nadir CD4 count, a detectable baseline viral load, previous PI experience, non-R5 tropism, having ≥3 active drugs in the accompanying regimen, and a more recent calendar year of maraviroc initiation.ConclusionsThis study reports on the largest observation cohort of patients who started maraviroc across 8 European countries. In this overall highly treatment-experienced population, with a small but appreciable subset that received maraviroc outside of standard treatment guidelines, maraviroc was safe and reasonably effective, with relatively low rates of discontinuation over 48 weeks and only 2 cases of serum transaminase elevations reported as reasons for discontinuation.

Highlights

  • Among antiretrovirals approved for the treatment of HIV-1 infection, maraviroc and the recently approved ibalizumab are unique in targeting a host protein rather than a viral enzyme

  • This study reports on the largest observation cohort of patients who started maraviroc across 8 European countries

  • As a result of the targeted mode of action, a tropism test demonstrating the presence of chemokine receptor 5 (CCR5)-tropic (R5) virus is a prerequisite for maraviroc use

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Summary

Introduction

Among antiretrovirals approved for the treatment of HIV-1 infection, maraviroc and the recently approved ibalizumab are unique in targeting a host protein rather than a viral enzyme. As a result of the targeted mode of action, a tropism test demonstrating the presence of CCR5-tropic (R5) virus is a prerequisite for maraviroc use. Tropism was determined with the Trofile phenotypic test provided by Monogram Biosciences (CA, USA). Largely retrospective validation studies established genotypic tropism testing as an alternative, based on the analysis of the gp120 V3 sequence through an automated predictive algorithm, most commonly the geno2pheno[coreceptor] system [1]. Comparative evaluations demonstrated a good albeit not perfect technical correlation between phenotypic and genotypic tropism testing [2,3,4]. Genotypic tropism testing was found to predict virological outcome within both retrospective evaluations of clinical trial data and in observational cohorts [2,5,6,7]

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