D/C/F/TAF is the first single pill protease inhibitor-based FDC. The formulation includes darunavir, cobicistat, FTC and tenofovir alafenamide.
Planned 24-week interim results from a 48-week phase 3 study were presented by Jean-Michel Molina from University of Paris, showing that switching to this FDC maintained undetectable viral load.1
This is a 48-week open-label, multicenter, non-inferiority study in 1141 participants who were already on boosted PI-based ART with TDF/FTC. Participants were randomised (2:1) to either switch to D/C/F/TAF (n=763) or continue on current ART (n=378). Enrolment criteria included having viral load <50 copies/mL for at least two months and eGFR that was >50 min/mL. Previous history of viral failure (reported in 15% of participants) was allowed so long as genotypic resistance to darunavir was not documented.
The primary endpoint is cumulative virologic rebound at week 48 (defined as confirmed ≥ 50 copies/mL or premature discontinuations, with last viral load ≥50 copies/mL). Non-inferiority was defined using relatively new criteria of 4% margin for 95% confidence interval.
This was a largely male, white study population in early HIV infection. Baseline characteristics included age 46 (range 19 to 78); 18% women/82% men and 75% white, 21% black. Median CD4 count was approximately 630 cells/mm3 (range: 111-1921) with 10% +< 350 cells/mm3. Current boosted-PI was darunavir (71%), atazanavir (22%) and lopinavir (8%) and approximately 40% were still on first-line ART.
At week 24, viral load was maintained < 50 copies/mL by 96.3% vs 95.5% of the D/C/F/TAF vs control groups respectively (difference 0.8; 95%CI -1.7 to +3.3%). Overall there were similar low rates of virologic failure (0.5% vs 0.8% respectively), with no discontinuations for viral failure and no detected resistance to any study drug.
The most common side effects (nasopharyngitis, upper respiratory tract infection and vitamin D deficiency) were mild and similar in each arm (approximately 7%, 6% and 5% respectively). Grade 3/4 laboratory changes were also not significantly different between groups.
However, small changes in bone mineral density at hip and spine, likely linked to switch from TDF to TAF were significant with small increases in the switch group and small continued loss in the TDF group remaining on current ART.
The study is still ongoing and 48-week data are needed to evaluate whether these promising early results are maintained for the primary virological endpoint. This is similarly important for longer-term results about side effects.
A second phase 3 study in treatment-naive participants is also currently ongoing.2
- Molina J-M 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.
- clinicaltrials.gov. A study to evaluate efficacy and safety of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC) versus a regimen consisting of darunavir/cobicistat FDC with emtricitabine/tenofovir disoproxil fumarate FDC. NCT02431247.