Five-days-on-two-days-off (FOTO) versus daily bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people with HIV: a pilot randomized clinical trial.

Objectives: This open-label, randomized clinical trial determined plasma bictegravir trough concentration (Ctrough) and compared virological efficacy with daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) versus BIC/FTC/TAF taken five-days-on-two-days-off (FOTO) in people with HIV (PWH).

Methods: Sixty PWH aged ≥20 years with plasma HIV RNA load (PVL) of <50 copies/mL for ≥6 months after having received daily BIC/FTC/TAF were randomized (1:1) to daily versus FOTO BIC/FTC/TAF. The primary endpoint was plasma bictegravir Ctrough above the in vitro protein-adjusted 95% effective concentration (162 ng/mL) at Weeks 4, 28 and 52. The secondary endpoints were PVL < 50 copies/mL and weight and renal and metabolic parameters at the same time points. After Week 52, all participants entered the 48-week extension phase to receive FOTO BIC/FTC/TAF.

Results: There were no significant differences in the baseline clinical characteristics, including drug-metabolizing gene polymorphisms, between the two groups. In the FOTO group, 90%, 93.3% and 100% of participants achieved a bictegravir Ctrough of >162 ng/mL at Weeks 4, 28 and 52, respectively. In intention-to-treat analysis, PVL of <50 copies/mL at Weeks 4, 28 and 52 was achieved by 100%, 93.3% and 100%, respectively, in the FOTO group, compared with 96.7%, 93.3% and 96.7% in the daily group. All five participants in the FOTO group with bictegravir Ctrough of <162 ng/mL at Weeks 4 and 28 maintained PVL <50 copies/mL. Of 57 (95.0%) participants who entered the extension phase, 56 (98.2%) completed the study and all maintained PVL <50 copies/mL at extension Week 48.

Conclusions: We showed PWH could successfully maintain sufficient bictegravir exposure and virological suppression with FOTO BIC/FTC/TAF.

Clinical trials registration: NCT06773754.