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Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients

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

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.
   
citation Olearo F, Nguyen H, Bonnet F, Yerly S, Wandeler G, Stoeckle M, Cavassini M, Scherrer A, Costagiola D, Schmid P, Günthard H F, Bernasconi E, Boeni J, D'arminio Monforte A, Zazzi M, Rossetti B, Neau D, Bellecave P, Rijnders B, Reiss P, Wit F, Kouyos R, Calmy A. Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients. Open Forum Infect Dis 2019; 6:ofz330.
   
type journal paper/review (English)
date of publishing 12-07-2019
journal title Open Forum Infect Dis (6/10)
ISSN print 2328-8957
pages ofz330
PubMed 31660328
DOI 10.1093/ofid/ofz330