Fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide might be a safe and efficacious alternative to continued boosted protease inhibitor therapy in adults with HIV-1 infection, according to a study recently published in The Lancet.
Boosted protease inhibitors have a high barrier to resistance and are a component of antiretroviral regimens used to treat HIV-1 infection. Regimens based on boosted darunavir or atazanavir are widely prescribed but have disadvantages, including the potential for drug interactions and side effects such as hyperbilirubinemia, gastrointestinal adverse effects (AEs), and lipohypertrophy. Bictegravir is a potent, unboosted integrase strand transfer inhibitor (INSTI) with a high barrier to resistance and low potential for drug interactions. In recent studies in adults infected with HIV-1 previously untreated with antiretroviral therapy, bictegravir was compared with dolutegravir.
Bictegravir was well tolerated and showed high rates of HIV-1 suppression without the development of resistance, when coformulated with emtricitabine and tenofovir alafenamide- 2 nucleoside reverse transcriptase inhibitors (NRTIs). Switching to this regimen also may avoid potential toxic effects of tenofovir disoproxil fumarate and abacavir. Additionally, patients may benefit from a once-daily, fixed-dose combination regimen, which can improve adherence and clinical and virological outcomes. Therefore, this phase 3, noninferiority trial (ClinicalTrials.gov identifier: NCT02603107) assessed the efficacy and safety of switching to a fixed-dose, once-daily combination of bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor therapy in virologically suppressed adults with HIV-1 infection.
Between 2015 and 2016, 577 patients infected with HIV (≥18 years old) were enrolled at 121 outpatient centers in 10 countries. Participants were eligible if they had an estimated glomerular filtration rate of ≥50 mL/min, had been virologically suppressed (plasma HIV-1 RNA <50 copies/mL) for ≥6 months before screening, and were on a regimen consisting of boosted atazanavir or darunavir plus either emtricitabine and tenofovir disoproxil fumarate or abacavir and lamivudine. Participants were randomly assigned (1:1) either to remain on their baseline boosted protease inhibitor regimen (n=287; herein known as the boosted protease inhibitor group) or switch to co-formulated once-daily bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) (n=290; herein known as the bictegravir group. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of ≥50 copies/mL at week 48.
At week 48, 2% of participants in the bictegravir group and 2% in the boosted protease inhibitor group had plasma HIV-1 RNA of ≥50 copies/mL; thus, switching to the bictegravir regimen was non-inferior to continued boosted protease inhibitor therapy. The overall incidence and severity of AEs was similar between both groups; although headache occurred more frequently in the bictegravir group, it did not lead to study discontinuation. A total of 80% of participants in the bictegravir group and 79% of participants in the boosted protease inhibitor group had an AE. Furthermore, 19% of participants in the bictegravir group had drug-related AEs compared with 2% in the boosted protease inhibitor group. Only 1% of participants in the bictegravir group and <1% in the boosted protease inhibitor group discontinued treatment because of AEs. Adverse events leading to study discontinuation in the bictegravir group were rash (n=1) and schizophrenia (n=1), which were treatment-related. Adverse events leading to discontinuation in the boosted protease inhibitor group were not treatment-related.
Overall, the study authors concluded that, “the fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide is an efficacious and well tolerated regimen for the initial and ongoing treatment of HIV-1 infection, offering the potential for reduced drug interactions and regimen simplification (from a multi-tablet to a single-tablet regimen, with one of the smallest tablet sizes among available single-tablet regimens).”
Disclosure: Funding was provided by Gilead Sciences, Inc.
Daar ES, DeJesus E, Ruane P, et al; Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial [published online June 17, 2018]. The Lancet. doi: 10.1016/S2352-3018(18)30091-2