Clinical use, efficacy, and durability of maraviroc for antiretroviral therapy in routine care: A European survey
Autoři:
Andrea De Luca aff001; Patrizio Pezzotti aff003; Charles Boucher aff004; Matthias Döring aff005; Francesca Incardona aff006; Rolf Kaiser aff008; Thomas Lengauer aff005; Nico Pfeifer aff005; Eugen Schülter aff008; Anne-Mieke Vandamme aff010; Maurizio Zazzi aff001; Anna Maria Geretti aff012;
Působiště autorů:
Department of Medical Biotechnologies, University of Siena, Siena, Italy
aff001; Unità Operativa Complessa Malattie Infettive, Azienda Ospedaliera Universitaria Senese, Siena, Italy
aff002; Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
aff003; Department of Viroscience, Erasmus Medical Center, Rotterdam, Netherlands
aff004; Max Planck Institute for Informatics, Saarland Informatics Campus, Saarbrücken, Germany
aff005; EuResist Network, Rome, Italy
aff006; InformaPRO, Rome, Italy
aff007; Institute of Virology, University of Cologne, Cologne, Germany
aff008; Department of Computer Science, University of Tübingen, Tübingen, Germany
aff009; Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Leuven, Belgium
aff010; Center for Global Health and Tropical Medicine, Unidade de Microbiologia, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal
aff011; Institute of Infection and Global Health, University of Liverpool, Liverpool, England, United Kingdom
aff012
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0225381
Souhrn
Objectives
The study aimed to survey maraviroc use and assess effectiveness and durability of maraviroc-containing antiretroviral treatment (ART) in routine practice across Europe.
Methods
Data 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.
Results
At 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.
Conclusions
This 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.
Klíčová slova:
Antimicrobial resistance – Antiretrovirals – Drug therapy – Europe – HIV-1 – Viral load – Viral tropism
Zdroje
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