Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudina/Dolutegravir Therapy in Human Immunodeficiency Virus Treatment-Experienced Patients.

Background 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. Methods Observational study from five 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 (two consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in 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 (IPW) 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 [IQR, 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 (11.2-79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 (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 (HR 1.27 [95% CI 0.35-4.59]; 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.