Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients
Year: 2019
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated. METHOD: This is an observational study from 5 European HIV cohorts among treatment-experienced adults with ≤50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population. RESULTS: We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154-441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2-79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4-21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35-4.59 and HR 1.66; 95% CI, 0.81-3.43, respectively). CONCLUSIONS: In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.
Source: Open Forum Infectious Diseases
DOI: 10.1093/ofid/ofz330
Authors: Flaminia Olearo, Huyen Nguyen, Fabrice Bonnet, Sabine Yerly, Gilles Wandeler, Marcel Stoeckle, Matthias Cavassini, Alexandra Scherrer, Dominique Costagiola, Patrick Schmid, Huldrych F Günthard, Enos Bernasconi, Jürg Boeni, Antonella D’arminio Monforte, Maurizio Zazzi, Barbara Rossetti, Didier Neau, Pantxika Bellecave, Bart Rijnders, Peter Reiss, Ferdinand Wit, Roger Kouyos, Alexandra Calmy
Institutions: University Hospital of Geneva, University of Zurich, University Hospital Zurich, Université de Bordeaux, Inserm, Centre Hospitalier Universitaire de Bordeaux, Bordeaux Population Health, University of Geneva, University of Bern, University Hospital of Bern, Institute of Social and Preventive Medicine, University Hospital of Basel, Centre Hospitalier Universitaire Vaudois, Sorbonne Université, Institut Pierre Louis d‘Épidémiologie et de Santé Publique, Kantonsspital St. Gallen, Ospedale regionale di Lugano, University of Milan, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, University of Siena, Azienda Ospedaliera Universitaria Senese, Erasmus MC, Erasmus University Rotterdam
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,053
Funders: National Science Foundation, Harry Frank Guggenheim Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universiteit van Amsterdam, Erasmus Universiteit Rotterdam, Ministerie van Volksgezondheid, Welzijn en Sport, Universitair Medisch Centrum Utrecht, Maastricht Universitair Medisch Centrum, Leids Universitair Medisch Centrum, Universitair Medisch Centrum Groningen, Radboud Universitair Medisch Centrum, Universität Zürich, Centre Hospitalier Universitaire de Bordeaux, Stichting HIV Monitoring
OpenAlex ID: W2960940959