The EMERALD Study is a Phase III, open-label, noninferiority study in which 1,141 patients with stable HIV suppression on a regimen comprising a boosted protease inhibitor plus TDF/FTC were randomized (2:1) to either switch to an investigational single-tablet regimen containing darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (D/C/F/TAF) or continue their baseline regimen. As has been reported, rates of HIV suppression to <50 copies/mL at 48 weeks were virtually identical in the two groups (95% and 94%, respectively), and no new PI, TFV, or FTC resistance mutations developed in patients with virologic failure.(1)
The EMERALD Study excluded subjects who had a history of virologic failure on a darunavir-containing regimen or had darunavir-associated resistance mutations but (unusually for a switch study) it allowed subjects who had experienced virologic failure on other regimens or whose virus had resistance mutations to ARVs other than darunavir. At CROI this year, researchers presented an important new analysis of virologic response to D/C/F/TAF based on subjects' history of virologic failure and previous ARV exposure.(F) Of the study participants, 15% had experienced virologic failure on past regimens (12% with NRTI failure, and 7% with PI failure), and 58% previously had been treated with 5 or more ARVs. In stratified analysis, neither a history of virologic failure nor the number of ARVs the patient had been exposed to in the past made any significant difference in rates of viral suppression to <50 copies/mL.
Clinical Bottom Line
This study does not give information about specific NRTI or PI mutations (or specific past ARV regimens) and their impact on the efficacy of D/C/F/TAF, but it is reassuring to know that this combination was effective in the setting of previous virologic failure and likely resistance at least to FTC. Its effectiveness in these patients likely derives from the robustness of boosted darunavir, and may be limited to robust boosted PIs (data on dolutegravir in similar scenarios are lacking). It should be noted that D/C/F/TAF is the only single-pill combination with data to support its use in patients with previous virologic failure and likely NRTI resistance. DRV/C/F/TAF is available in Europe and is expected to be approved in the United States later this year.
1. Orkin C, Molina JM, Negredo N, et al; EMERALD Study Group. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV. 2018 Jan;5(1):e23-e34.
2. Eron JJ, Orkin C, Molina JM, et al. Analysis of HIV patients switching to D/C/F/TAF by prior ARV treatment experience. In: Program and abstracts of the 2018 Conference on Retroviruses and Opportunistic Infections; March 4-7, 2018; Boston. Abstract 502.