Bictegravir Combination Regimen Non-inferior to Boosted Protease Inhibitors in HIV

New findings from a phase 3 study showed a fixed-dose combination of bictegravir and emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was non-inferior to boosted protease inhibitor (bPI)-based regimens in virologically suppressed adults with HIV.

Included in the phase 3 study 1878 were 577 virologically-suppressed adults with HIV who were receiving boosted atazanavir (ATV) or darunavir (DRV) plus abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF), according to a press release.

The participants were randomized 1:1 to either continue their bPI regimen or switch to open-label co-formulated BIC/FTC/TAF once daily. At week 48, switching to BIC/FTC/TAF was found to be non-inferior to continuing bPI treatment, with 1.7% of patients in each arm having HIV-1 RNA ≥50 c/mL.

There were 92.1% of patients in the BIC/FTC/TAF arm who had HIV-1 RNA ≥50 c/mL, and 88.9% in the bPI arm, according to the release.

“These data demonstrate the potential of BIC/FTC/TAF to match the efficacy of a boosted protease inhibitor regimen while also offering a high barrier to resistance and fewer interactions with other drugs,” said lead author Eric Daar, MD, in the release. “The findings, along with data from 3 other phase 3 studies in both treatment-experienced and treatment-naïve patients, suggest that the investigational regimen of BIC/FTC/TAF may be appropriate for a broad range of people living with HIV.”

There were no reports of patients in the BIC/FTC/TAF arm developing treatment-emergent resistance. Only 1 participant on DRV/ritonavir plus ABC/3TC developed a treatment-emergent NRTI mutation associated with abacavir.

In the BIC/FTC/TAF arm, there were no reports of renal adverse events (AEs) leading to discontinuations or cases of proximal renal tubulopathy. The incidence of grade 3 or 4 AEs were 4% in the BIC/FTC/TAF arm compared with 6% in the bPI arm, according to the report. Incidence of grade 3 or 4 laboratory abnormalities were 6% for the BIC/FTC/TAF arm versus 29% for the bPI arm.

The most common AEs in both arms were headache, diarrhea, nasopharyngitis, and upper respiratory tract infection.

“The combination of unboosted integrase inhibitor with the FTC/TAF backbone has the potential to further evolve HIV triple therapy with convenient dosing in a single-tablet regimen,” Norbert W. Bischofberger, PhD, executive vice president of Research and Development and chief scientific officer at Gilead, said in the release. “We look forward to the opportunity to offer patients this next-generation therapy as part of our TAF-based portfolio of treatments for HIV.”

A New Drug Application for BIC/FTC/TAF was filed on June 12, 2017, and the treatment was granted Priority Review. The FDA set a target action date of February 12, 2018. Additionally, a marketing application for BIC/FTC/TAF is under review in the European Union and was validated by the European Medicines Agency on July 13, 2017, according to the release.