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Open Forum Infect Dis. 2019 Jul 12;6(10):ofz330. doi: 10.1093/ofid/ofz330. eCollection 2019 Oct.

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

Author information

1
Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Switzerland.
2
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Switzerland.
3
Institute of Medical Virology, Swiss National Reference Centre for Retroviruses, University of Zurich, Switzerland.
4
University of Bordeaux, Institut de Santé Publique d'Epidémiologie et de Développement (ISPED), U1219 INSERM, France.
5
Centre Hospitalier Universitaire de Bordeaux, Service de Médecine Interne et Maladies Infectieuses, France.
6
Laboratory of Virology, Geneva University Hospitals and Faculty of Medicine, Switzerland.
7
Institute of Social and Preventive Medicine, University Hospital of Bern, Switzerland.
8
Division of Infectious Diseases, University Hospital of Basel, Switzerland.
9
Division of Infectious Diseases, Lausanne University Hospital, Switzerland.
10
INSERM, Sorbonne Université, Institut Pierre Louis d'Épidémiologie et de Santé Publique, Paris, France.
11
Division of Infectious Diseases and Hospital Epidemiology, St. Gallen Cantonal Hospital, Switzerland.
12
Division of Infectious Diseases, Ospedale Regionale di Lugano, Switzerland.
13
Department of Health Sciences, Institute of Infectious and Tropical Medicine, L'Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, University of Milan, Italy.
14
Department of Medical Biotechnology, University of Siena, Italy.
15
Infectious Diseases Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
16
Virology Laboratory, Centre Hospitalier Universitaire de Bordeaux, France.
17
Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.

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.

KEYWORDS:

ABC/3TC/DTG; M184V/I; treatment-experienced patients; virological failure

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