Background: Integrase strand transfer inhibitors (INSTIs) are widely recommended for initial HIV-1 treatment. Bictegravir (BIC, B) is a novel, once-daily INSTI with potent antiviral activity being developed in coformulation with emtricitabine and tenofovir alafenamide (F/TAF).
Methods: In this Phase 2 study, treatment naïve, HIV-infected adults were randomized 2:1 to receive blinded treatment with BIC or dolutegravir (DTG) coadministered with open label F/TAF (200/25 mg). After all participants completed 48 weeks, they were unblinded and switched to a single fixed-dose combination tablet of B/F/TAF 50/200/25 mg. The proportion of participants with HIV-1 RNA <50 copies/mL (c/mL) was assessed at Week (W) 24 and W48 of the blinded phase and 12 weeks after switching to open label B/F/TAF (W72).
Results: Of 98 participants enrolled in the blinded treatment phase, 65 were randomized to BIC+F/TAF and 33 to DTG+F/TAF. Most were male, had asymptomatic HIV infection, with median HIV-1 RNA 4.4-4.5 log10 c/mL. The proportion of subjects with HIV-1 RNA <50 c/mL at W24 was 97% for the BIC arm and 94% for the DTG arm, and at W48 was 97% and 91%, respectively (Table). All 92 participants who completed the blinded phase were switched to B/F/TAF at W60. At W72 or 12 weeks after switching to open-label B/F/TAF, 99% (91/92) maintained HIV-1 RNA <50 c/mL (98% prior BIC arm [N=62]; 100% prior DTG arm [N=30]) and one individual withdrew prior to the analysis. No viral resistance was detected in participants treated with BIC. No participants discontinued open label B/F/TAF due to an adverse event, there were no treatment-related serious adverse events and no deaths. One individual on BIC previously discontinued due to an adverse event of urticaria following the W24 visit.
Conclusion: All participants switched from DTG+F/TAF to open-label B/F/TAF maintained virologic suppression, with none discontinuing due to adverse events. During 72 weeks of follow-up, no treatment-emergent resistance to any components was detected in participants taking B/F/TAF. B/F/TAF demonstrated durable virologic suppression in naïve patients through W72 and was safe and effective after switching from DTG + F/TAF, further study in treatment naïve and experienced populations is warranted.
BMS: Consultant and Investigator , Consulting fee , Research grant and Research support
GlaxoSmithKline/ViiV: Consultant and Investigator , Consulting fee , Research grant and Research support
AbbVie: Consultant , Consulting fee
Janssen: Consultant , Consulting fee
Merck: Consultant , Consulting fee
Janssen: Consultant , Investigator and Speaker's Bureau , Consulting fee and Speaker honorarium
G. Crofoot, Gilead: Investigator and Scientific Advisor , Advisory honorarium and Research grant
ViiV: Investigator and Scientific Advisor , Advisory honorarium , Research grant and Research support
D. Ward, Gilead: Investigator , Research support
P. Benson, Gilead Sciences: Investigator , Shareholder and Speaker's Bureau , Research support and Speaker honorarium
ViiV Healthcare: Investigator , Research support
L. Wei, Gilead: Employee and Shareholder , Salary
K. White, Gilead Sciences, Inc.: Employee and Shareholder , Salary
S. Collins, Gilead: Employee and Shareholder , Salary
H. Martin, Gilead Sciences: Employee , Salary
A. Cheng, Gilead: Employee and Shareholder , Salary
E. Quirk, Gilead: Employee and Shareholder , Salary