Department of Health and Human Services Adults and Adolescents Antiretroviral Guidelines Panel* Classifies a Fixed-Dose Combination Product of Bictegravir/Tenofovir Alafenamide/Emtricitabine as One of the Recommended Initial Regimens for Most People with HIV

Date: March 27, 2018

Introduction

Bictegravir (BIC) is a new HIV-1 integrase strand transfer inhibitor (INSTI) that has been approved by the U.S. Food and Drug Administration for initial therapy in adults with HIV as part of a single-tablet, once-daily regimen that includes tenofovir alafenamide and emtricitabine (BIC/TAF/FTC).¹ BIC/TAF/FTC is not recommended for individuals with creatinine clearance <30 mL/min or with severe liver impairment. It is not approved for persons younger than 18 years of age, and there is insufficient safety information regarding its use in pregnant women.

On the basis of clinical trial results, the Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) recommends the use of BIC/TAF/FTC 50/25/200 mg once daily as one of the Recommended Initial Regimens for Most People with HIV (AI).

Clinical Trial and Safety Data for BIC/TAF/FTC as an Initial Antiretroviral Regimen

The efficacy of BIC in antiretroviral therapy (ART)-naive adults with HIV has been evaluated in two large, Phase 3, randomized, double-blinded clinical trials. These trials compared BIC to dolutegravir (DTG), with both drugs administered in combination with two nucleoside reverse transcriptase inhibitors (NRTIs). The primary efficacy endpoint was the proportion of participants with plasma HIV RNA <50 copies/mL at Week 48.

• The GS-US-380-1490 trial randomized participants 1:1 to receive either BIC/TAF/FTC or DTG with coformulated TAF/FTC. Both regimens were given once daily. At Week 48, 89% of participants in the BIC arm and 93% of participants in the DTG arm achieved HIV RNA <50 copies/mL (P = 0.12).²
• The GS-US-380-1489 trial randomized subjects 1:1 to receive BIC/TAF/FTC or coformulated DTG/abacavir/lamivudine (DTG/ABC/3TC) once daily. At Week 48, 92.4% of participants in the BIC/TAF/FTC arm and 93.0% of participants in the DTG/ABC/3TC arm achieved HIV RNA <50 copies/mL (P = 0.78).³
• The most commonly reported adverse reactions associated with BIC/TAF/FTC were nausea, diarrhea, and headache.

Other Factors and Considerations

The following drug interactions should be considered when BIC is used in combination with other medications:¹

• BIC is a cytochrome P (CYP) 3A4 and a uridine diphosphate glucuronosyltransferase (UGT) 1A1 substrate, and its metabolism may be affected by concomitant use of a CYP3A4 and UGT1A1 inducer or inhibitor. Rifampin or other rifamycins may decrease BIC or TAF concentrations, which may result in loss of therapeutic effect. BIC/FTC/TAF should not be used in patients who require rifamycins. Certain anticonvulsants and St. John’s Wort should also be avoided.¹
• BIC is an inhibitor of the drug transporters OCT2 and MATE1, which may lead to increased concentrations of drugs that are substrates of these transporters. For this reason, dofetilide is contraindicated with BIC/TAF/FTC.
• BIC is not a CYP3A4 inducer or inhibitor; therefore, unlike elvitegravir/cobicistat, it is unlikely to affect the metabolism of medications that are CYP3A4 substrates.
• As with other INSTIs, oral absorption of BIC may be reduced when it is coadministered with polyvalent cations (e.g., aluminum-, magnesium-, or calcium-containing antacids, or calcium or iron supplements). See product label for dosing recommendations when BIC is used with these products.¹

BIC decreases tubular secretion of creatinine without affecting glomerular function; increases in serum creatinine are typically observed within the first 4 weeks (the median increase is 0.10 mg/dL after 48 weeks). This effect on creatinine secretion is similar to that of some other medications used in people with HIV, including DTG and cobicistat.

Treatment-emergent mutations that confer BIC resistance have not yet been reported in people receiving BIC for initial therapy. BIC has not been studied in people with prior INSTI failure or INSTI-associated drug resistance mutations, and BIC should not be used for these individuals until more data are available.

Based on data from randomized switch trials, BIC/TAF/FTC is also indicated in people who have suppressed virus, have been on a stable antiretroviral regimen for at least 3 months, and have no history of treatment failure or resistance to TAF, FTC, 3TC, or INSTIs.^1,4

Summary

BIC/TAF/FTC is an effective and well-tolerated INSTI-based regimen for initial therapy in adults with HIV, with efficacy that is noninferior to DTG/ABC/3TC and DTG plus TAF/FTC for up to 48 weeks. On the basis of these clinical trial results, the Panel classifies BIC/TAF/FTC as one of the Recommended Initial Regimens for Most Adults with HIV (AI).

* The Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents is a working group of the Office of AIDS Research Advisory Council (OARAC), National Institutes of Health, in Bethesda, Maryland.

References

1. Bictegravir/tenofovir alafenamide/emtricitabine [package insert]. Gilead Sciences. 2018. Available at: http://www.gilead.com/~/media/files/pdfs/medicines/hiv/biktarvy/biktarvy_pi.pdf.
2. 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;390(10107):2073-2082. Available at: http://www.ncbi.nlm.nih.gov/pubmed/28867499.
3. 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;390(10107):2063-2072. Available at: http://www.ncbi.nlm.nih.gov/pubmed/28867497.
4. Daar E, DeJesus E, Ruane P, et al. Phase 3 randomized, controlled trial of switching to fixed-dose bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) from boosted protease inhibitor-based regimens in virologically suppressed adults: Week 48 results. Presented at: ID Week. 2017. San Diego, CA. Available at: https://idsa.confex.com/idsa/2017/webprogram/Paper67504.html.