A key opinion leader reviews findings presented at ID Week 2020 from a post-hoc analysis of the AMBER study comparing GI tolerability of D/C/F/TAF to TDF.
Moti Ramgopal, MD, FACP, FIDSA, CPI: The AMBER study looked at D/C/F/TAF [darunavir, cobicistat, emtricitabine, tenofovir alafenamide] versus TDF [tenofovir disoproxil fumarate]. This was the first single-tablet boosted protease inhibitor [PI] study that we have, and looking at ritonavir versus non-ritonavir boosted PI. Defining it, this is a post-hoc analysis looking after the clinical trial was completed; it looked back at all of these data points. When we look at this, we found, this is a naive treatment study, and this was a registrational study as well, but for Symtuza, which we call D/C/F/TAF [darunavir, cobicistat, emtricitabine, tenofovir alafenamide].
In treatment-naive patients, the incidence and prevalence of D/C/F/TAF [darunavir, cobicistat, emtricitabine, tenofovir alafenamide] or Symtuza-related GI AEs [gastrointestinal adverse events] were low. They tended to present early in the study, and they rapidly decreased over time. The incidence of diarrhea was less than 1% at the start of week 2. Previously associated with protease inhibitors, we saw higher instances of diarrhea with previous medications. This was quite interesting that the instance of diarrhea was quite low, less than 1% at the start of week 2.
The median duration of GI-related AEs was 16.5 days. This was much higher in other PI-based regimens. We had 1 to 2 AEs, including nausea, abdominal discomfort, and flatulence. Even though there was GI discomfort in AEs, the grades were much lower, and the severity and the incidences were also quite lower.
The question’s going to be, what are the clinical implications of these data? The clinically implications, knowing that PIs were previously associated with GI complaints or GI symptomology, now we’ve seen that this is much lower than we previously expected. This implies that 1 single-tablet protease regimen, which is Symtuza or D/C/F/TAF [darunavir, cobicistat, emtricitabine, tenofovir alafenamide], is tolerable. It has a short duration of the AEs, and the AEs are of lower severity. The common perception of poor GI tolerability of PIs is now changing. From this post-hoc analysis, it shows that this is a concept that needs to be changed in our thought process.