Drugs

Bictegravir

Bictegravir

Other Names: BIC, GS-9883, bictegravir sodium Drug Class: Integrase Inhibitors Molecular Formula: C21 H18 F3 N3 O5 Registry Number: 1611493-60-7 (CAS) Chemical Name: 2,5-Methanopyrido(1',2':4,5)pyrazino(2,1-b)(1,3)oxazepine-10-carboxamide, 2,3,4,5,7,9,13,13a-octahydro-8-hydroxy-7,9-dioxo-N-((2,4,6-trifluorophenyl)methyl)-, (2R,5S,13aR)- Organization: Gilead Sciences, Inc. Phase of Development: Bictegravir is a component of the fixed-dose combination product bictegravir/emtricitabine/tenofovir alafenamide (brand name: Biktarvy), which received marketing approval for the treatment of HIV infection by the U.S. Food and Drug Administration in February 2018.

It is unclear whether stand-alone bictegravir will be developed, although a Phase 2 trial of an investigational NRTI (GS-9131) will evaluate GS-9131 plus stand-alone bictegravir and boosted darunavir as an optimized ART regimen.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 Gilead Sciences press release,3 and HIV Treatment Bulletin article4)

What is bictegravir?

What is bictegravir?

Bictegravir is a component of the fixed-dose combination (FDC) tablet Biktarvy, which has been approved by the Food and Drug Administration (FDA) to treat HIV infection.3 Bictegravir is also being studied separately as an investigational drug to treat HIV infection.

Bictegravir belongs to a group of HIV drugs called integrase inhibitors.2 Integrase inhibitors block an HIV enzyme called integrase. By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body.

In vitro studies have shown that bictegravir may be effective against strains of HIV that are no longer affected by other HIV medicines.5-7

To learn about how investigational drugs are tested during clinical trials, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

Which clinical trials are studying bictegravir?

Which clinical trials are studying bictegravir?

Bictegravir Single-Agent Tablet

Study Names: GS-US-442-4148; NCT03472326
Phase: 2
Status: This study is ongoing, but not recruiting participants.
Location: Uganda
Purpose: The purpose of this study is to evaluate the effectiveness of using GS-9131 in participants who are currently on an HIV treatment regimen that is not controlling their HIV infection. The researchers will also investigate the effectiveness of an HIV treatment regimen that includes GS-9131, bictegravir, darunavir, and ritonavir.8

Bictegravir/Emtricitabine/Tenofovir Alafenamide FDC Tablet (Biktarvy)

Biktarvy was approved by the FDA in February 2018. Approval was based on supporting data from the following Phase 3 trials.3

Study Names: GS-US-380-1490; NCT02607956
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Location: North America, Australia, Europe
Purpose: The purpose of this study is to compare the safety and effectiveness of Biktarvy to that of dolutegravir plus emtricitabine/tenofovir alafenamide (brand name: Descovy) in people with HIV who have never taken HIV medicines before.9

Study Names: GS-US-380-1489; NCT02607930
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Location: North America and Europe
Purpose: The purpose of this study is to compare the safety and effectiveness of Biktarvy to that of abacavir/dolutegravir/lamivudine (brand name: Triumeq) in people with HIV who have never taken HIV medicines before.10

Study Names: GS-US-380-1844; NCT02603120
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Location: North America, Australia, Europe
Purpose: The purpose of this study is to evaluate the effectiveness of switching to Biktarvy versus continuing on an HIV treatment regimen that consists of dolutegravir, abacavir, and lamivudine in people whose HIV is well controlled by their current HIV medicines.11

Study Names: GS-US-380-1878; NCT02603107
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Location: North America, Australia, Europe
Purpose: The purpose of this study is to evaluate the effectiveness of switching to Biktarvy versus continuing on a regimen that consists of boosted atazanavir or boosted darunavir plus either emtricitabine/tenofovir disoproxil fumarate (brand name: Truvada) or abacavir/lamivudine (brand name: Epzicom) in people whose HIV is well controlled by their current HIV medicines.12

For more details on the studies listed above, see the Health Professional version of this drug summary.

ClinicalTrials.gov lists several other planned studies, ongoing late-stage studies, or post-approval studies that are evaluating the effectiveness of Biktarvy. Notably, a Phase 4 study (NCT03499483) will evaluate whether Biktarvy can prevent HIV infection in adults after high-risk sexual contact (non-occupational post-exposure prophylaxis).13

What side effects might bictegravir cause?

What side effects might bictegravir cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of bictegravir listed above.

GS-US-380-1490 (NCT02607956):
In this Phase 3 study, three participants in the Biktarvy group stopped treatment because of drug-related side effects—one stopped treatment due to chest pain, one due to abdominal swelling, and one due to sleep problems, indigestion, headache, and depressed mood. Most of the side effects that occurred during the study were mild or moderate in severity. Some of the most common side effects reported among participants in the Biktarvy group were headaches, diarrhea, nausea, common cold, and fatigue.14

GS-US-380-1489 (NCT02607930):
In this Phase 3 study, no participants in the Biktarvy group stopped treatment because of a side effect. The majority of side effects that occurred during the study were mild or moderate in severity. Some of the most common side effects among participants in the Biktarvy group were nausea, diarrhea, headache, upper respiratory tract infection, and common cold.15

GS-US-380-1844 (NCT02603120):
In this Phase 3 study, five participants who received Biktarvy stopped treatment because of a drug-related side effect. Two participants stopped treatment due to headaches, one due to abnormal dreams, one due to stroke, and one due to vomiting. Overall, most of the side effects that occurred during the study were mild or moderate in severity. Some of the most common side effects reported among participants in the Biktarvy group were upper respiratory tract infection, common cold, headache, diarrhea, and joint pain.16

GS-US-380-1878 (NCT02603107):
In this Phase 3 study, drug-related side effects occurred more frequently among participants in the Biktarvy group than among participants in the group that received boosted atazanavir or boosted darunavir. These Biktarvy-related side effects were mostly mild or moderate in severity. Other drug-related side effects that occurred among participants in the Biktarvy group were headache, flatulence, nausea, and diarrhea.17

Additional information on side effects known to be associated with bictegravir can be found in the FDA-approved Biktarvy Full Prescribing Information.

Because bictegravir is still being studied, information on possible side effects of the drug is not complete. As testing of bictegravir continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying bictegravir?

Where can I get more information about clinical trials studying bictegravir?

More information about bictegravir-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: bictegravir. https://chem.nlm.nih.gov/chemidplus/rn/1611493-60-7. Accessed July 17, 2019
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed July 17, 2019
  3. Gilead: Press Release, dated February 7, 2018. U.S. Food and Drug Administration approves Gilead’s Biktarvy® (bictegravir, emtricitabine, tenofovir alafenamide) for treatment of HIV-1 infection. https://www.gilead.com/news/press-releases/2018/2/us-food-and-drug-administration-approves-gileads-biktarvy-bictegravir-emtricitabine-tenofovir-alafenamide-for-treatment-of-hiv1-infection. Accessed July 17, 2019
  4. Collins S and Clayden P. HIV pipeline 2018: new drugs in development. HIV Treatment Bulletin. 2018 Jul; 19(1) Suppl: 1-29. http://i-base.info/htb/wp-content/uploads/2018/07/PIPELINE-2018-full-version.pdf. Accessed July 17, 2019
  5. White K, Cihlar T, Miller MD. Potent activity of bictegravir (BIC; GS-9883), a novel unboosted HIV-1 integrase strand transfer inhibitor (INSTI), against patient isolates with INSTI-resistance. American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. http://www.natap.org/2016/HIV/062316_02.htm. Accessed July 17, 2019
  6. Jones G, Goldsmith J, Mulato A, et al. Bictegravir (GS-9883), a novel HIV-1 integrase strand transfer inhibitor (INSTI) with optimized in vitro resistance profile. American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. Levin: Bictegravir (GS-9883), a novel HIV-1 integrase strand transfer inhibitor (INSTI) with optimized in vitro resistance profile; National AIDS Treatment Advocacy Project (NATAP); HIV Articles; 2016. http://www.natap.org/2016/HIV/062016_03.htm. Accessed July 17, 2019
  7. Lazerwith S, Cai R, Chen X, et al. Discovery of GS-9883, an HIV-1 integrase strand transfer inhibitor (INSTI) with improved pharmacokinetics and in vitro resistance profile. American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. Levin: Discovery of bictegravir (GS-9883), a novel, unboosted, once-daily HIV-1 integrase strand transfer inhibitor (INSTI) with improved pharmacokinetics and in vitro resistance profile; National AIDS Treatment Advocacy Project (NATAP); HIV Articles; 2016. http://www.natap.org/2016/HIV/062016_05.htm. Accessed July 17, 2019
  8. Gilead Sciences. A Phase 2 study to evaluate the efficacy of GS-9131 functional monotherapy in HIV-1-infected adults failing a nucleos(t)Ide reverse transcriptase inhibitor-containing regimen with nucleos(t)Ide reverse transcriptase inhibitor resistant virus, followed by continued treatment with a GS-9131+bictegravir+darunavir+ritonavir regimen. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 8, 2018. NLM Identifier: NCT03472326. https://clinicaltrials.gov/ct2/show/NCT03472326. Accessed July 17, 2019
  9. Gilead Sciences. A Phase 3, randomized, double-blind study to evaluate the safety and efficacy of GS-9883/emtricitabine/tenofovir alafenamide versus dolutegravir + emtricitabine/tenofovir alafenamide in HIV-1 infected, antiretroviral treatment-naive adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02607956. https://clinicaltrials.gov/ct2/show/NCT02607956. Accessed July 17, 2019
  10. Gilead Sciences. A Phase 3, randomized, double-blind study to evaluate the safety and efficacy of GS-9883/emtricitabine/tenofovir alafenamide versus abacavir/dolutegravir/lamivudine in HIV-1 infected, antiretroviral treatment-naive adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02607930. https://clinicaltrials.gov/ct2/show/NCT02607930. Accessed July 17, 2019
  11. Gilead Sciences. A Phase 3, randomized, double-blind study to evaluate the safety and efficacy of switching from a regimen of dolutegravir and ABC/3TC, or a fixed-dose combination (FDC) of ABC/DTG/3TC to a FDC of GS-9883/F/TAF in HIV-1 infected subjects who are virologically suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02603120. https://clinicaltrials.gov/ct2/show/NCT02603120. Accessed July 17, 2019
  12. Gilead Sciences. A Phase 3, randomized, open-label study to evaluate the safety and efficacy of switching from regimens consisting of boosted atazanavir or darunavir plus either emtricitabine/tenofovir or abacavir/lamivudine to GS-9883/emtricitabine/tenofovir alafenamide in virologically suppressed HIV-1 infected adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 10, 2015. NLM Identifier: NCT02603107. https://clinicaltrials.gov/ct2/show/NCT02603107. Accessed July 17, 2019
  13. Fenway Community Health. A Phase IV open-label evaluation of safety, tolerability, and acceptability of a fixed-dose formulation of bictegravir, emtricitabine/tenofovir alafenamide (B/F/TAF) for non-occupational prophylaxis following potential exposure to HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 9, 2018. NLM Identifier: NCT03499483. https://clinicaltrials.gov/ct2/show/NCT03499483. Accessed July 17, 2019
  14. 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. doi:10.1016/S0140-6736(17)32340-1
  15. 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. doi:10.1016/S0140-6736(17)32299-7
  16. Molina J-M, 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;5(7):e357-e365. doi:10.1016/S2352-3018(18)30092-4
  17. 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;5(7):e347-e356. doi:10.1016/S2352-3018(18)30091-2

Last Reviewed: July 17, 2019

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