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.

References

• 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.