Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) improved kidney and bone markers in a subanalysis focused on people 50 years old or older in a randomized, double-blind, placebo-controlled trial. Participants switching to TAF maintained viral control.
Coformulated with emtricitabine (FTC, Emtriva), TAF/FTC is licensed as a component of antiretroviral regimens that may be used in patients with an estimated glomerular filtration rate (eGFR) as low as 30 mL/min. Because tenofovir levels in blood are lower with TAF than TDF, less drug should reach off-target sites where it can cause side effects.
Study 311-1089 randomized people with a viral load below 50 copies/mL while taking TDF/FTC (Truvada) plus a third agent (except in a single-tablet regimen) to maintain TDF/FTC or switch to TAF/FTC. Everyone had an eGFR ≥50 mL/min. Daily TAF/FTC doses were 10/200 mg with a ritonavir-boosted protease inhibitor and 25/200 mg with an unboosted third agent.
The subanalysis presented at IDWeek/IDSA 2016 involved 150 participants randomized to switch to TAF/FTC and 144 randomized to stay with TDF/FTC. Median ages of the TAF and TDF groups were 55 and 54, proportions of women were 11% and 13% and proportions of whites were 79% and 84%, respectively. Median eGFR stood above 90 mL/min in both groups.
A week-48 snapshot analysis determined that 96% randomized to TAF/FTC and 94% randomized to TDF/FTC had a viral load below 50 copies/mL at that point. No one randomized to TAF/FTC and one person randomized to TDF/FTC met virologic failure criteria. CD4 counts rose marginally in both study arms.
Ten percent of participants in each group had a drug-related adverse event, no one assigned to TAF/FTC and 1% assigned to TDF/FTC had a drug-related grade 3 or 4 adverse event, and 3% on TAF/FTC versus 1% on TDF/FTC stopped treatment because of an adverse event. The five adverse events leading to discontinuation in the TAF/FTC group were atrial fibrillation, dysphagia, peripheral edema, insomnia/altered mood and overdose.
Higher proportions assigned to TAF/FTC than TDF/FTC had a grade 3 or 4 increase in fasting low-density lipoprotein (LDL) cholesterol (6% versus 2%) and fasting total cholesterol (3% versus <1%), results reflecting the cholesterol-lowering effect of TDF. At 48 weeks, total-to-high-density lipoprotein cholesterol ratio did not differ between study arms. Through 48 weeks, triglycerides rose to a higher level with TAF/FTC than TDF/FTC (median 127 versus 115 mg/dL, P = .065).
Median eGFR through 48 weeks rose (improved) more with TAF/FTC than with TDF/FTC (8.8 versus 2.5 mL/min, P < .001). Four urine markers of renal safety improved with TAF/FTC while worsening with TDF/FTC (P < .001 for all differences). Mean changes in bone mineral density through 48 weeks favored TAF/FTC in the spine (+1.9% versus -0.2%, P < .001) and hip (+1.0% versus -0.3%, P < .001). Renal and bone marker changes in the two study arms were similar in participants 50 or older and in participants younger than 50.
Based on these results, the researchers proposed that TAF/FTC "is an important [antiretroviral] backbone for older patients living with HIV."