Emtricitabine/tenofovir DF (F/TDF) is a standard-of-care nucleoside reverse transcriptase inhibitor (NRTI) backbone due to its favorable efficacy and safety profile. However, TDF can be associated with renal and bone toxicities. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug that achieves 91% lower plasma tenofovir levels than TDF. In elvitegravir/cobicistat/F/TAF phase 3 studies, TAF had less adverse effect on kidneys and bone than TDF.
We conducted a 96-week (wk) randomized, double blind, active controlled study in virologically suppressed HIV-1 infected patients receiving F/TDF-containing regimens to evaluate the efficacy and safety of switching from F/TDF to F/TAF vs continuing F/TDF while remaining on the same third agent. Primary endpoint was virologic success at Wk 48 by ITT FDA snapshot algorithm with a pre-specified noninferiority margin of 10%. We describe the Wk 48 data.
663 patients were randomized and treated (F/TAF 333 vs F/TDF 330); median age 49 years, 15% women, median estimated glomerular filtration rate (eGFR) 100 mL/min. 46% were on a boosted protease inhibitor, 28% on an integrase inhibitor, 25% on a non-NRTI. Through Wk 48, virologic success (HIV-1 RNA <50 c/mL) was maintained in most patients in both treatment groups: F/TAF 94.3% vs F/TDF 93.0% (difference +1.3%, 95% CI: -2.5% to +5.1%), demonstrating noninferiority of F/TAF to F/TDF (Table). Emergent resistance was rare (0.3% vs 0). Drug related serious adverse events were rare (0 vs 0.3%). Drug discontinuation due to adverse events (AEs) was low (2.1% vs 0.9%). There were no cases of proximal renal tubulopathy in either group. Median eGFR improved by +8.4 mL/min in the F/TAF group vs by +2.8 mL/ min in the F/TDF group (P <0.001). Quantitative measures of proteinuria improved in the F/TAF group but not in the F/TDF group (Table). Bone mineral density (BMD) increased in the F/TAF group but declined in the F/TDF group: hip (mean) +1.14% vs -0.15% (P <0.001) and spine +1.53% vs -0.21% (P <0.001), respectively. More patients in the F/TAF group had ≥ 3% improvement in BMD at Wk 48: hip 17% vs 9% and spine 30% vs 14%.
In virologically suppressed patients switching from F/TDF to F/TAF, high rates of virologic suppression were maintained, while renal and bone safety parameters improved. With its safety benefits relative to F/TDF, F/TAF has the potential to become an important NRTI backbone for antiretroviral treatment.