Impact of the M184V/I mutation on the efficacy of abacavir / lamivudine / dolutegravir therapy in human immunodeficiency virus treatment-experienced patients. Open Forum Infectious Diseases
Olearo et al. aimed to conduct a prospective study using data from 5 large HIV cohorts in four European countries (France, Italy, the Netherlands and Switzerland) to assess the efficacy of the ABC/3TC/DTG (Triumeq®) regimen in virologically-suppressed, antiretroviral therapy (ART-) experienced patients, with or without a previously documented M184V/I mutation. The primary outcome was the time to first virological failure (VF) (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in ART). They also analyzed a composite outcome considering the presence of VF and/or virological blips.
The study included 1’626 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 1’000 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).
In conclusion, in this large international prospective study, there was an extremely low rate of VF among treatment-experienced patients receiving an ABC/3TC/DTG regimen, irrespective of the presence of a M184V/I mutation. Furthermore, no new mutations were observed in reverse transcriptase or integrase after VF in any of the patients in which genotyping was successfully performed, with the caveat that the genotypic resistance results were available for only a minority of patients (6 of 21). Additional analyses are required to demonstrate whether these findings will remain robust during an extended observation period.