Phase 3 Randomized, Controlled Trial of Switching to Fixed-dose Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) from Boosted Protease Inhibitor-based Regimens in Virologically Suppressed Adults: Week 48 Results

Abstract

Background: Boosted protease inhibitor regimens (bPIs) are effective and often used in HIV‐infected individuals with difficulties with adherence, but they can have drug‐drug interactions and GI adverse effects. Bictegravir (B), a novel, potent integrase strand transfer inhibitor with a high barrier to resistance and low potential for drug‐drug interactions, was coformulated with the recommended nucleoside reverse transcriptase inhibitor backbone emtricitabine (FTC)/tenofovir alafe‐namide (F/TAF) and demonstrated high efficacy and tolerability in randomized studies in treatment‐naïve adults. This randomized Phase 3 study assesses efficacy and safety of switching to B/F/TAF from a multi‐tablet regimen containing a bPI. Materials and methods: HIV‐infected adults suppressed on regimens of boosted atazanavir (ATV) or darunavir (DRV) + abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF), were randomized 1:1 to continue their current bPI regimen or switch to open‐label coformulated B/F/TAF (50/200/25 mg) once daily. Primary endpoint was proportion with HIV‐1 RNA ≥50 copies/ml (c/ml) at W48 (FDA snapshot). Non‐inferiority was assessed through 95.002% confidence intervals (CI) using a margin of 4%. Secondary endpoints included proportion with HIV‐1 RNA <50 c/ml and safety measures at W48. Results: Five hundred and seventy‐seven participants were randomized and treated with B/F/TAF (n = 290) or current bPI regimens (n = 287): 17% women, 26% Black, median age 48 years. Most were receiving a bPI with FTC/TDF (85%) at screening. At W48, switching to B/F/TAF was non‐inferior to continuing bPI with 1.7% in each group having HIV‐1 RNA >50 c/ml (difference‐0.0%; 95.002%CI‐2.5% to 2.5%, p = 1.00); the proportion with HIV‐1 RNA <50 c/ml was 92.1% in B/F/TAF vs 88.9% in bPI. No participant on B/F/TAF developed resistance to study drugs. One participant on DRV/ritonavir + ABC/3TC developed a treatment‐emergent L74V mutation. Incidence of grade 3 or 4 AEs was similar (B/F/TAF 4%, bPI regimens 6%). No renal discontinuations or tubulopathy cases occurred with B/F/TAF. Conclusions: Adults switching to B/F/TAF from a boosted PI maintained high rates of virologic suppression without resistance. B/F/TAF was safe and well tolerated.