The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide might provide a safe and efficacious option for ongoing treatment of HIV-1 infection, according to a study recently published in the Lancet.
Integrase strand transfer inhibitors are recommended for first-line antiretroviral therapy in combination with 2 nucleoside or nucleotide reverse transcriptase inhibitors.
Bictegravir is a novel, potent unboosted integrase strand transfer inhibitor with a high in vitro barrier to resistance and low potential for drug interactions. Previous studies show that bictegravir plus emtricitabine and tenofovir alafenamide regimen was well tolerated in virologically suppressed adults with HIV-1 infection and shows high rates of HIV-1 suppression without virological failure resulting from treatment-emergent resistance.
With that said, fixed-dose, combination bictegravir, emtricitabine, and tenofovir alafenamide might be a potent, convenient, tolerable, and practical regimen for long-term treatment in many patients with HIV-1 infection, and switching to this regimen may maintain high rates of suppression and avoid potential adverse effects of abacavir, such as cardiovascular events, and other adverse effects on the central nervous system that have been reported with dolutegravir in clinical practice. Therefore, this noninferiority, phase 3 trial (ClinicalTrials.gov identifier: NCT02603120) investigated the efficacy and safety of switching to fixed-dose, combination bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir, abacavir, and lamivudine in virologically suppressed adults with HIV-1 infection.
Between 2015 and 2016, 646 HIV-1-infected adults (aged ≥18 years) were enrolled at 96 outpatient centers in 9 countries. Eligible participants received a regimen of 50 mg dolutegravir, 600 mg abacavir, and 300 mg lamivudine (fixed-dose combination or multitablet regimen), had an estimated glomerular filtration rate of ≥50 mL/min, and had been virologically suppressed (plasma HIV-1 RNA <50 copies per mL) for ≥3 months before screening. Participants were randomly assigned to either switch to the bictegravir group and receive coformulated bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg; n=282) or continue in the dolutegravir group, receiving dolutegravir, abacavir, and lamivudine (n=281) once daily for a median of 49.9 weeks. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of ≥50 copies/mL at week 48.
Results showed that switching to the bictegravir regimen was noninferior to continuing to receive dolutegravir, abacavir, and lamivudine for the primary outcome. Three[ALH1] [ND2] participants in the bictegravir group had HIV-1 RNA ≥50 copies/mL during the study vs 1 participant in the dolutegravir group (difference, 0.7%; P =.62). Changes in hip and lumbar spine bone mineral densities were not significantly different between treatment groups, nor were changes in renal function parameters.
Both treatments were well tolerated, and most adverse effects were mild in severity. Treatment-related adverse effects were recorded in 8% of participants in the bictegravir group and 16% of participants in the dolutegravir group. Treatment was discontinued because of adverse events in 2% of participants in the bictegravir group and in 1% of participants in the dolutegravir group.
Overall, the study authors conclude, “Our findings suggest that the tolerability profile for bictegravir, emtricitabine, and tenofovir alafenamide is similar to that of dolutegravir, abacavir, and lamivudine, including in measures of bone, renal, and lipid safety.”
Disclosure: Funding was provided by Gilead Sciences.
Molina JM, Ward D, Brar I, et al; Switching to fixed-dose bicegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet. 2018;5(7):e357-e365.