Bictegravir

Bictegravir (INN; BIC, formerly known as GS-9883)^[1][2] is a second-generation integrase inhibitor (INSTI) class that was structurally derived from an earlier compound dolutegravir by scientists at Gilead Sciences. In vitro and clinical results were presented by Gilead in the summer of 2016.^[3][4] In 2016, bictegravir was in a Phase 3 trial as part of a single tablet regimen in combination with tenofovir alafenamide (TAF) and emtricitabine (FTC) for the treatment of HIV-1 infection.^[5]

Bictegravir

Clinical data
Other names	GS-9883
ATC code	None
Identifiers
IUPAC name (1S,11R,13R)-5-Hydroxy-3,6-dioxo-N-(2,4,6-trifluorobenzyl)-12-oxa-2,9-diazatetracyclo[11.2.1.0~2,11~.0~4,9~]hexadeca-4,7-diene-7-carboxamide
CAS Number	1611493-60-7 as salt: 1807988-02-8
PubChem CID	90311989
DrugBank	DB11799 as salt: DBSALT002077
ChemSpider	44208822 as salt: 48772870
UNII	8GB79LOJ07 as salt: 4L5MP1Y7W7
KEGG	D10909 as salt: D10910
ChEBI	CHEBI:172943
ChEMBL	ChEMBL3989866 as salt: ChEMBL3989867
CompTox Dashboard (EPA)	DTXSID701027937
Chemical and physical data
Formula	C21H18F3N3O5
Molar mass	449.386 g·mol−1
3D model (JSmol)	Interactive image
SMILES c1c(cc(c(c1F)CNC(=O)c2cn3c(c(c2=O)O)C(=O)N4[C@H]5CC[C@H](C5)O[C@@H]4C3)F)F
InChI InChI=1S/C21H18F3N3O5/c22-9-3-14(23)12(15(24)4-9)6-25-20(30)13-7-26-8-16-27(10-1-2-11(5-10)32-16)21(31)17(26)19(29)18(13)28/h3-4,7,10-11,16,29H,1-2,5-6,8H2,(H,25,30)/t10-,11+,16+/m0/s1 Key:SOLUWJRYJLAZCX-LYOVBCGYSA-N

The combination drug bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) was approved for use in 2018 in Australia,^[6] the European Union^[7] and the United States^[8] and in 2019 in New Zealand^[9] and the United Kingdom;^[10] a generic version was approved by the Drugs Controller General of India in 2019.^[11] As of 2024,^[update] it is recommended as a first-line choice of antiretroviral therapy in several countries, including the European Union,^[12] the United Kingdom^[13] and the United States.^[14]

Medical use

Bictegravir is used a in fixed dose combination with tenofovir alafenamide and emtricitabine for the treatment of HIV-1 infection.^[4][15]

Contraindication

Bictegravir should not be used with dofetilide and rifampin.^[16] Use of dofetilide with bictegravir increases the concentration of dofetilide, which can lead to life-threatening events.^[16] Concomitant use of bictegravir and rifampin causes significant interactions because of an effect rifampin has on bictegravir.^[16] Bictagravir is metabolized primarily through the liver (CYP3A4), so inducers of CYP3A4 should be avoided.^[4]

Adverse effects

The most common side effects seen in bictegravir use include diarrhea, nausea, and headache.^[4]

Society and culture

Economics

In February 2022, Gilead agreed to pay ViiV Healthcare over $1 billion to settle patent infringement cases.^[17][18]

References

1. "Recommended INN: List 75" (PDF). WHO Drug Information. 30 (1): 102. 2016. Archived (PDF) from the original on 4 November 2021. Retrieved 4 October 2020.
2. "Bictegravir - Gilead Sciences". Adis Insight. Springer Nature Switzerland AG. Archived from the original on 2 February 2017. Retrieved 22 January 2017.
3. Highleyman L (6 July 2016). "New integrase inhibitor bictegravir looks promising in early studies". NAM aidsmap. Archived from the original on 2 February 2017. Retrieved 20 January 2017.
4. Zeuli J, Rizza S, Bhatia R, Temesgen Z (November 2019). "Bictegravir, a novel integrase inhibitor for the treatment of HIV infection". Drugs of Today. 55 (11): 669–682. doi:10.1358/dot.2019.55.11.3068796. PMID 31840682. S2CID 209385285. Archived from the original on 28 August 2023. Retrieved 28 August 2023.
5. "Gilead Presents Preliminary Data on Bictegravir, an Investigational Integrase Strand Transfer Inhibitor for the Treatment of HIV" (Press release). Gilead Sciences. 20 June 2016. Archived from the original on 2 February 2017. Retrieved 20 January 2017.
6. "Australian Public Assessment Report for Bictegravir / Emtricitabine / Tenofovir alafenamide" (PDF). Therapeutic Goods Administration. 1 August 2019. Retrieved 22 February 2024.
7. "Biktarvy". European Medicines Agency. 21 June 2018. Retrieved 22 February 2024.
8. "U.S. Food and Drug Administration Approves Gilead's Biktarvy (Bictegravir, Emtricitabine, Tenofovir Alafenamide) for Treatment of HIV-1 Infection" (Press release). Gilead Sciences. 7 February 2018.
9. "BIKTARVY Data Sheet v 8.0" (PDF). Medsafe. 24 August 2023. Retrieved 22 February 2024.
10. "Bictegravir-emtricitabine-tenofovir alafenamide for the treatment of HIV-1 in adults". NHS England. 17 July 2019. Retrieved 22 February 2024.
11. "Hetero launches TAFFIC, the latest 3-in-1 single pill for HIV treatment" (Press release). Hetero Drugs. 17 December 2019. Retrieved 22 February 2024.
12. "Initial Regimens: ART-naïve Adults". European AIDS Clinical Society. October 2023. Retrieved 22 February 2024.
13. "BHIVA guidelines on antiretroviral treatment for adults living with HIV-1 2022 (2023 interim update)" (PDF). British HIV Association. 28 May 2023. p. 16. Retrieved 22 February 2024.
14. "Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV" (PDF). HIV.gov. 21 September 2022. p. 6. Retrieved 22 February 2024.
15. Wohl DA, Yazdanpanah Y, Baumgarten A, Clarke A, Thompson MA, Brinson C, et al. (June 2019). "Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial". The Lancet. HIV. 6 (6): e355–e363. doi:10.1016/S2352-3018(19)30077-3. PMID 31068270. S2CID 148570850. Archived from the original on 29 January 2022. Retrieved 29 January 2022.
16. "Biktarvy - FDA Prescribing Highlights" (PDF). Archived (PDF) from the original on 26 July 2021. Retrieved 29 January 2022.
17. "GSK announces settlement between ViiV Healthcare and Gilead Sciences, Inc. resolving litigation relating to Biktarvy and ViiV's dolutegravir patents and entry into a patent licence agreement". ViiV Healthcare (Press release). ViiV Healthcare. Retrieved 26 August 2023.
18. "GSK announces settlement between ViiV Healthcare and Gilead Sciences, Inc. resolving litigation relating to Biktarvy and ViiV's dolutegravir patents and entry into a patent licence agreement". GSK US (Press release). 1 February 2022. Retrieved 28 August 2023.

Further reading

• Tsiang M, Jones GS, Goldsmith J, Mulato A, Hansen D, Kan E, et al. (December 2016). "Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile". Antimicrobial Agents and Chemotherapy. 60 (12): 7086–7097. doi:10.1128/AAC.01474-16. PMC 5118987. PMID 27645238.