The EMERALD and AMBER Trials in HIV

William Short, MD, MPH, AAHIVS: We’ve had something historic. In July of 2017 we had another single tablet regimen approved which was coformulated—darunavir, cobicistat, emtricitabine, and tenofovir alafenamide. And it’s listed as SYMTUZA. It’s the first time we’ve had a single tablet regimen that contained the protease inhibitor. And the registrational trials that went about to approve that drug were the AMBER and the EMERALD trials.

AMBER looked at patients who were antiretroviral naïve, and basically randomized them to receive the components of Symtuza—which again was darunavir, COBI [cobicistat], emtricitabine, and tenofovir alafenamide versus darunavir with cobicistat—and then fixed dose tenofovir disoproxil fumarate and emtricitabine, and compared them. The results showed that it was noninferior and it was very well tolerated. Again, showing that the components of that single tablet regimen were just as good as the combination drug. So comparing a two-drug regimen to one, which a lot of patients want for simplicity. That was the AMBER trial.

The EMERALD trial looked at antiretroviral treatment experienced patients. So these patients had been exposed to drugs in the past. When they entered the trial they had to be on antiretrovirals. They had to be suppressed, meaning their viral load had to be less than undetectable, whatever undetectable was defined as in the trial. And they had to be at that level for greater than or equal to 6 months. And then they made a switch.

They either stayed on their current regimen or they switched to the components of SYMTUZA, or darunavir/COBI, emtricitabine, and then tenofovir alafenamide. One of the interesting things about this trial as opposed to other switch trials, in most of the switch trials you have to enter with no evidence of drug resistance. In this, that was the one thing that stood out for inclusion criteria. You could have evidence of drug resistance or have failed regimens. And when you look at the baseline characteristics of the patients, a good percentage of these patients had been on more than 5 antiretroviral agents.

You have a really good idea that here’s someone who comes in, they have experience with a certain amount of drugs, and then you make that switch. And really what the switch showed is that patients maintained their viral suppression. What I like about that trial is it gives me confidence in someone who’s coming in and maybe I don’t have their background records, I don’t have all their genotypes, I can feel confident making that switch and allowing them to maintain their virologic suppression. They were 2 really great trials that were done in 2 different populations looking at some of the newer therapies.