Integrase strand transfer inhibitors (INSTIs), when combined with 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs), make up the bulk of first-line HIV therapy regimens. With over 30 drugs approved for the treatment of HIV infection, the regimen choice is often determined by concerns over pill burden, tolerability and/or toxicity, and barrier to resistance.
Biktarvy is a fixed-dose, single-tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide. It received FDA approval on February 7, 2018, for treatment-naïve patients with HIV or those already virologically suppressed on an antiretroviral therapy regimen for at least 3 months with no known resistance to any of the drug components. Two of the 3 drug components, emtricitabine and tenofovir alafenamide, are already part of other first-line therapy regimens and are known to be safe and well tolerated by most patients. Biktarvy is a new, highly active INSTI with both a high barrier to resistance and few drug–drug interactions. These advantages have allowed Biktarvy to quickly become a regimen of choice among HIV health care providers.
Biktarvy was studied in 4 phase 3 trials, 2 intreatment-naïve patients who were HIV-1 positive and 2 in virologically suppressed patients. Study 1489 was a noninferiority trial that randomized 629 treatment-naïve adults 1:1 to either Biktarvy or abacavir/dolutegravir/lamivudine (Triumeq) for 144 weeks. The primary end point was HIV viral load of less than 50 at week 48, and the noninferiority margin was set at 12%. The end point was achieved in 92.4% of patients receiving Biktarvy and 93.0% in those in the abacavir/dolutegravir/lamivudine group, with a difference of 0.6% (CI, –4.8 to 3.6). Neither group had any documented resistance to the study drugs. Interestingly, patients in the Biktarvy group had fewer adverse effects, mainly because of lower rates of nausea (5% vs 17%, respectively; P
Study 1490 compared Biktarvy to combination dolutegravir/emtricitabine/tenofovir alafenamide (Tivicay and Descovy). This study was again conducted in treatment-naïve adults who were HIV-1 positive, with the same primary end point of HIV viral load of less than 50 at the end of 48 weeks with a noninferiority margin of 12%. A total of 657 adults were randomized 1:1 to Biktarvy or dolutegravir/emtricitabine/tenofovir alafenamide. At week 48, 89% of patients in the Biktarvy group and 93% in the dolutegravir group met the predetermined end point (difference of 3.5%; CI –7.9 to 1.0), which met noninferiority criteria. No resistance emerged in either group. The adverse effects were similar between the 2 groups, with headache and gastrointestinal upset being the most common.2
The other 2 studies evaluated switching adults who were HIV-1 positive and already stably virally suppressed on a different regimen to Biktarvy. Study 1878 evaluated 577 patients on a stable boosted protease inhibitor plus a dual-NRTI backbone regimen and then randomized half of them to switch to Biktarvy. The individuals had to be on their prior regimen for at least 6 months and have a viral load of less than 50 for at least 6 months. They could not have had previous exposure to other INSTIs. Biktarvy was being compared with a regimen of either boosted atazanavir or darunavir with a backbone of tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine. The patients were randomized 1:1 to either group, with the primary end point being the proportion of patients at week 48 with a viral load of 50 or higher. In each group, 5 subjects had a viral load of 50 or higher at week 48 (2%).3
Finally, study 1844 assessed switching from abacavir/dolutegravir/lamivudine in virologically suppressed patients to Biktarvy. The study randomized patients 1:1 to either agent and assessed an end point of virological failure using viral loads of 50 or higher at 48 weeks. This occurred in 3 of 248 patients (1%) in the Biktarvy group and 1 of 281 (<1%) in the abacavir/dolutegravir/lamivudine arm.4
ADVERSE REACTIONS AND PRECAUTIONS
Multiple considerations need to be addressed before prescribing Biktarvy. It is not recommended in patients with a creatinine clearance of less than 30 or in those with severe hepatic impairment. Although drug interactions are minimal, Biktarvy cannot be given concomitantly with rifampin or dofetilide. Furthermore, clinicians must follow guideline recommendations to test patients for hepatitis B prior to use because emtricitabine and tenofovir alafenamide are components. This remains as a black box warning for abrupt discontinuation of this medication in patients with hepatitis B, as it can lead to severe and acute exacerbations.5
PLACE IN THERAPY
Biktarvy represents another advance in the treatment of HIV infection. Studies support Biktarvy as a safe and effective new HIV therapy. As we continue to improve our options for HIV management, it is understandable that providers are increasingly turning to Biktarvy over the other first-line regimens. Biktarvy requires no additional lab testing (eg, for HLA-B27), a limit of other first-line agent abacavir/dolutegravir/lamivudine. The high barrier of resistance and once-daily formulation, along with no restrictions on taking it with or without food, make it particularly attractive for many of our patients. Additionally, Biktarvy remains a good alternative for virologically suppressed patients who are on more
Matt is a board-certified internal medicine physician in her second year of infectious disease fellowship at Temple University Hospital in Philadelphia, Pennsylvania. She completed her medical education at Philadelphia College of Osteopathic Medicine and her Internal Medicine Residency at Lankenau Medical Center in Wynnewood, Pennsylvania.
- Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2063-2072. doi: 10.1016/S0140-6736(17)32299-7.
- Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2073-2082. doi: 10.1016/S0140-6736(17)32340-1.
- 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. Lancet HIV. 2018 Jul;5(7):e347-e356. doi: 10.1016/S2352-3018(18)30091-2.
- Molina JM, Ward D, Brar I, et al. Switching to fixed-dose bictegravir, 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 HIV. 2018 Jul;5(7):e357-e365. doi: 10.1016/S2352-3018(18)30092-4.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Integrase strand transfer inhibitor-based regimens [February 25, 2019] [F-19, table 8B]