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On the Way: The First Protease Inhibitor-Based Single-Tablet Regimen
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On the Way: The First Protease Inhibitor-Based Single-Tablet Regimen

The EMERALD Study is a Phase 3 randomized (2:1), open-label, noninferiority study examining the strategy of switching patients with suppressed HIV RNA on a regimen consisting of a boosted protease inhibitor plus tenofovir disoproxil fumarate (TDF)/emtricitabine to an investigational single-tablet regimen containing darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (D/C/F/TAF). At the 9th IAS Conference on HIV Science, researchers presented a 24-week interim analysis of their findings.

In the study, 763 subjects switched to the D/C/F/TAF single tablet and 378 participants continued their current regimens. Subjects could not have a history of virologic failure on a darunavir-containing regimen or a darunavir-associated resistance mutation. Most were taking darunavir (71%) or atazanavir (22%) at study enrollment, and 15% were using cobicistat as a pharmacokinetic booster. Small proportions of women (18%) and black patients (21%) were enrolled. Only 10% of participants had CD4+ cell counts of <350 cells/µL.

At 24 weeks, 96.3% of subjects remained virologically suppressed in the D/C/F/TAF arm, and 95.5% in the control arm. Virologic failure in occurred in 0.5% of the switch participants (n = 4) and 0.8% of the continuation participants (n = 3); there was no emergent resistance to any of the components of D/C/F/TAF. There were no significant differences between groups in rates of serious adverse events or in study discontinuation due to adverse events. The D/C/F/TAF group experienced a very small increase in glomerular filtration rate (GFR) (as measured by cystatin C), while control participants had a small decrease in GFR (+0.3 vs -1.0 mL/min/1.73 m2). Bone mineral density (BMD) at the hip and spine increased in D/C/F/TAF patients and declined in controls. The differences between groups in both estimated GFR and BMD changes were statistically significant.

Clinical Bottom Line

This study of D/C/F/TAF is planned to continue for a total of 48 weeks, followed by an extension phase. D/C/F/TAF also is being studied in ARV-naive patients, and more data should be reported in coming months. Based on currently available data, use of this first single-tablet regimen to include a protease inhibitor probably will be limited to treatment-naive or "lightly experienced" populations; further study will be needed to determine its potential utility in minimizing pill burden for more treatment-experienced patients, its pharmacokinetics during pregnancy, and its efficacy and impact in persons coinfected with hepatitis.

Molina JM, Gallant J, Orkin C, et. al. Efficacy and safety of switching from boosted-protease inhibitor plus emtricitabine/tenofovir disoproxil fumarate regimens to the single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in virologically-suppressed, HIV-1-infected adults through 24 weeks: EMERALD study. In program and abstracts of the 9th IAS Conference on HIV Science; July 23-26, 2017; Paris, France. Oral abstract TUAB0101.
Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Regimen Versus Boosted Protease Inhibitor (bPI) Along With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) Regimen in Virologically-Suppressed, HIV-1 Infected Participants.