Switch study shows F/TAF non-inferior to continuing abacavir/3TC

Results from the first randomised study comparing FTC/tenofovir alafenamide (F/TAF) to continuing on abacavir/3TC showed little significant differences between the newer vs older dual NRTI combinations, but also no risk from switching.

This was a randomised, double-blind, placebo controlled switching study in 556 participants on ABC/3TC-based ART, sponsored by Gilead. Week-48 primary endpoint results were presented by Alan Winston from Imperial College, London. Entry criteria included viral suppression <50 copies/mL on ABC/3TC-based ART for > 6 months and CrCl > 50 mL/min.

Baseline criteria included median age 52 years (range: 20 to 79). 18% women, 73% white, with high CD4 counts (median >650 cells/mm³). Although renal function was good, with median eCrCl 100 mL/min (IQR: 83 to 123), approximately half the cohort had hyperlipidaemia, 40% had hypertension, 12% had diabetes and 6% were defined as having cardiovascular disease. Participants had been taking abacavir/3TC for a median of 8 years (IQR: 3 to 11). The third component of ART was an NNRTI for 50%, with 30% using PI and 20% integrase-based ART.

By week-48, there were fewer overall discontinuations in the abacavir/3TC arm (n=18 vs 31; 7% vs 11%), mainly die to higher loss to follow-up or investigation decision (both n= 0 vs 3).

Viral efficacy <50 copiers/mL at week-48 was also higher for the abacavir/3TC group at 93% vs 90% (difference -3.0%; 95%CI: -8.2 to +2.0) but this met the criteria for non-inferiority (based on lower margin of –10% cut off).

Side effects were generally low incidence and grade and closely similar in both groups. Laboratory abnormalities were also similar, including lipid changes.

However, although changes in estimated creatinine clearance favoured F/TAF (1.1 vs +1.3 mL/min; p=0.05), there were no significant differences in renal tubular biomarkers or bone mineral density. Small differences in some lipid parameters didn’t results in a significant difference in TC:HDL ratio or in new use of lipid lowering drugs.

The single death was sudden cardiac event in the F/TAF arm that was not judged linked to ART.

Comment

This randomised dataset is interesting, even with no expected benefits in renal and bone markers. Further follow-up will continue to week-96.

The difference in cost (approximately 4000 vs 500 Euros a year) was raised in the Q&A session afterwards as likely to limit widespread switching in clinical practice, unless there is concern for cardiovascular risk.

Winston A et al. Phase 3 randomized controlled trial of switching to emtricitabine/tenofovir alafenamide (F/TAF) from abacavir/lamivudine (ABC/3TC) in virologically suppressed adults: week 48 results. EACS 2017, Milan. Oral abstract PS8/4.