by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
February 4, 2020
Orkin, C et al. on behalf of the AMBER study group. Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-naïve HIV-1 patients. AIDS: December 10, 2019 – Volume Publish Ahead of Print
The AMBER trial is a phase 3, double-blind, non-inferiority study conducted at numerous sites in the United States, Canada and Europe. Participants included treatment naïve HIV-1 infected adults with a baseline viral load of ≥1000 copies/mL and a CD4+ count >50 cells/mm3. 725 patients were randomized to single-tablet darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) or darunavir/cobicistat (D/C) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) > 48 weeks. After week 48, patients taking the two-tablet PI-based regimen could continue this therapy or switch to single-tablet D/C/F/TAF for the subsequent 48 weeks. At week 96 of the trial, by intention-to-treat analysis, 85% of patients in the single-tablet arm had viral loads <50 copies/mL and 83.7% of patients in the two-tablet (control) group were undetectable at <50 copies/mL. Among those subjects who were not fully suppressed at 96 weeks, there were no darunavir or tenofovir-associated resistance mutations seen. During the study, only 3% of patients receiving D/C/F/TAF stopped therapy due to adverse events and only 1% of those switched therapy after week 48. Stability or improvements in renal function and bone mineral density was maintained in the D/C/F/TAF arm and occurred in patients who switched therapy from TDF to single-tablet TAF-containing therapy. Changes in lipids including increase in total cholesterol/HDL-cholesterol ratio at week 96 were not significantly changed from baseline although increases in total cholesterol were slightly higher in the TAF-containing arm.
In the most recent DHHS guidelines the “Recommended Initial Regimens” are now INSTI-based. The guidelines do include DRV/c or DRV/r plus TAF or TDF with (FTC or 3TC) (AI) under “Recommended Initial Regimens in Certain Clinical Situations.” For those individuals who begin ART before resistance test results are available, boosted DRV is an appropriate choice because the rate of transmitted PI resistance is low and DRV has a high barrier to resistance. The main disadvantage is the risk of drug-drug interactions, especially with cobicistat or ritonavir. There is also reassuring data from the EMERALD study with D/C/F/TAF that included treatment-experienced patients who were switched to this single-tablet regimen. Virologic response rates ranged from 91-97%.
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