Dolutegravir

Dolutegravir
Clinical data
Pronunciation/ˌdoʊluːˈtɛɡrəvɪər/
DOH-loo-TEG-rə-veer
Trade namesTivicay, Tivicay PD, others
Other namesDTG, GSK572, S-349572
AHFS/Drugs.comMonograph
MedlinePlusa613043
License data
Pregnancy
category
  • AU: B1
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only
  • UK: POM (Prescription only)
  • US: ℞-only
  • EU: Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailabilityn/a
Protein binding≥98.9%
MetabolismUGT1A1 and CYP3A
Elimination half-life~14 hours
ExcretionFeces (53%) and urine (18.9%)
Identifiers
  • (4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.237.735 Edit this at Wikidata
Chemical and physical data
FormulaC20H19F2N3O5
Molar mass419.385 g·mol−1
3D model (JSmol)
  • C[C@@H]1CCO[C@@H]2N1C(=O)c3c(c(=O)c(cn3C2)C(=O)NCc4ccc(cc4F)F)O
  • InChI=1S/C20H19F2N3O5/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28)/t10-,15+/m1/s1
  • Key:RHWKPHLQXYSBKR-BMIGLBTASA-N

Dolutegravir, sold under the brand names Tivicay and Tivicay PD, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential exposure. It is taken by mouth.

Common side effects include trouble sleeping, feeling tired, diarrhea, high blood sugar, and headache. Severe side effects may include allergic reactions and liver problems. It is unclear if use during breastfeeding is safe. Dolutegravir is an HIV integrase strand transfer inhibitor which blocks the functioning of HIV integrase which is needed for viral replication.

Dolutegravir was approved for medical use in the United States in 2013. It is on the World Health Organization's List of Essential Medicines. Single tablet regimen combination drugs containing dolutegravir, such as dolutegravir/rilpivirine, dolutegravir/lamivudine, and abacavir/dolutegravir/lamivudine, are also available. As of 2019, the World Health Organization (WHO) recommends dolutegravir as the first- and second-line treatment for all persons with HIV.

Medical use

In the United States, dolutegravir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults (treatment-naïve or -experienced) and in children (treatment-naïve or -experienced but integrase strand transferase inhibitor (INSTI)-naïve) weighing at least 2 kilograms (4.4 lb); or in combination with rilpivirine as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen for at least six months with no history of treatment failure or known substitutions associated with resistance to either antiretroviral agent.

Dolutegravir is approved for use in a broad population of HIV-infected patients. It can be used to treat HIV-infected adults who have never taken HIV therapy (treatment-naïve) and HIV-infected adults who have previously taken HIV therapy (treatment-experienced), including those who have been treated with other integrase strand transfer inhibitors. Tivicay is also approved for children ages 12 years and older weighing at least 40 kilograms (kg) who are treatment-naïve or treatment-experienced but have not previously taken other integrase strand transfer inhibitors.

In the European Union, dolutegravir is indicated, in combination with other antiretroviral medicinal products, for the treatment of HIV-infected adults, adolescents and children above six years of age and weighing at least 14 kilograms (31 lb); or in combination with other antiretroviral medicinal products for the treatment of HIV-infected adults, adolescents and children at least four weeks of age or older and weighing at least 3 kilograms (6.6 lb).

In June 2020, the indication for dolutegravir in the US was expanded to include children at least four weeks old and weighing at least 3 kg (6.61 pounds).

Adverse effects

Common side effects of dolutegravir in clinical trials included insomnia and headache. Serious side effects included allergic reactions and abnormal liver function in patients who were also infected with hepatitis B or C. The package insert warns against a mean rise in serum creatinine of 0.11 mg/dL due to inhibition of tubular secretion of creatinine and does not affect renal function (GFR).

Pregnancy

Concerns that usage during pregnancy can result in harm to the baby have been refuted by studies that show there is no statistical difference in neural tube defects from the usage of dolutegravir compared with other antiretrovirals.

Dolutegravir is the US National Institutes of Health preferred antiretroviral drug for pregnant or non-pregnant people trying to conceive.

History

In February 2013, the US Food and Drug Administration (FDA) announced that it would fast track dolutegravir's approval process. In August 2013, dolutegravir was approved for medical use in the United States. In November 2013, dolutegravir was approved by Health Canada. In January 2014, dolutegravir was authorized for medical use in the European Union.

In June 2020, dolutegravir was approved in the United States with an indication to treat HIV-1 infection in children at least four weeks old and weighing at least 3 kilograms (6.6 lb) in combination with other antiretroviral treatments. It is intended to treat children at least four weeks old and 3 kilograms (6.6 lb) who have never been treated for HIV or who have been treated, but not with an integrase strand transferase inhibitor (INSTI) class drug.

The US Food and Drug Administration (FDA) granted the approval of Tivicay and Tivicay PD to ViiV Healthcare.

Society and culture

In April 2024, the government of Colombia issued its first ever compulsory license to invalidate the patent of Dolutegravir. Access to dolutegravir was enabled by a license to the Medicines Patent Pool however Colombia was not a listed territory. UNAIDS supported the move to enable a compulsory license decision. ViiV Healthcare disagreed with the decision on the use of the compulsory license by the government of Colombia. A separate agreement with the Medicines Patent Pool permits the distribution of generic versions of the medicine in Colombia, but it is restricted to children.

Climate change

Dolutegravir, used by 24 million people in low- and middle-income countries, has significantly reduced carbon emissions compared to the previous standard of care, efavirenz. This is the first report to analyze the environmental impact of a widely used medicine compared to its alternative. According to Unitaid, this transition will prevent over 26 million tons of CO2 from entering the atmosphere between 2017 and 2027, equivalent to eliminating 10 years of carbon emissions from Geneva, Switzerland.

References

  1. ↑ "Dolutegravir (Tivicay) Use During Pregnancy". Drugs.com. 16 October 2018. Retrieved 13 February 2020.
  2. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  3. ↑ "Drug and medical device highlights 2018: Helping you maintain and improve your health". Health Canada. 14 October 2020. Retrieved 17 April 2024.
  4. ↑ "Tivicay 50 mg Film-Coated Tablets Summary of Product Characteristics (SmPC)". emc. 14 October 2025. Retrieved 25 August 2026.
  5. 1 2 3 4 5 6 "Tivicay PD- dolutegravir sodium tablet, for suspension; Tivicay- dolutegravir sodium tablet, film coated". DailyMed. 29 October 2025. Retrieved 25 August 2026.
  6. 1 2 3 4 "Tivicay EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 13 February 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. 1 2 British national formulary: BNF 69 (69 ed.). British Medical Association. 2015. p. 429. ISBN 978-0-85711-156-2.
  8. 1 2 3 4 5 6 7 "Dolutegravir Sodium Monograph for Professionals". Drugs.com. Retrieved 20 April 2019.
  9. ↑ World Health Organization (2025). The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. Geneva: World Health Organization. doi:10.2471/B09474. hdl:10665/382243. License: CC BY-NC-SA 3.0 IGO.
  10. ↑ Sever B, Otsuka M, Fujita M, Ciftci H (March 2024). "A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication". International Journal of Molecular Sciences. 25 (7). doi:10.3390/ijms25073659. PMC 11012182. PMID 38612471.
  11. ↑ Ciccullo A, Baldin G, Borghetti A, Di Giambenedetto S (April 2020). "Dolutegravir plus lamivudine for the treatment of HIV-1 infection". Expert Review of Anti-infective Therapy. 18 (4): 279–292. doi:10.1080/14787210.2020.1729742. PMID 32067525. S2CID 211160876.
  12. ↑ Patel R, Evitt L, Mariolis I, Di Giambenedetto S, d'Arminio Monforte A, Casado J, et al. (August 2021). "HIV Treatment with the Two-Drug Regimen Dolutegravir Plus Lamivudine in Real-world Clinical Practice: A Systematic Literature Review". Infectious Diseases and Therapy. 10 (4): 2051–2070. doi:10.1007/s40121-021-00522-7. PMC 8572911. PMID 34426899.
  13. ↑ "WHO recommends dolutegravir as preferred HIV treatment option in all populations". World Health Organization (WHO) (Press release). Retrieved 22 July 2019.
  14. ↑ "FDA Approves Drug to Treat HIV Infection in Newborns". U.S. Food and Drug Administration (FDA). 25 August 2026. Retrieved 25 August 2026.
  15. ↑ "FDA approves new drug to treat HIV infection". U.S. Food and Drug Administration (FDA) (Press release). 12 August 2013. Archived from the original on 8 February 2014.
  16. 1 2 3 4 "FDA Approves Drug to Treat Infants and Children with HIV". U.S. Food and Drug Administration (FDA) (Press release). 12 June 2020. Archived from the original on 12 June 2020. Retrieved 12 June 2020.
  17. ↑ "U.S. FDA approves GlaxoSmithKline's HIV drug Tivicay". Reuters. 12 August 2013. Retrieved 13 February 2020.
  18. ↑ Gill MM, Khumalo P, Chouraya C, Kunene M, Dlamini F, Hoffman HJ, et al. (September 2023). "Strengthening the Evidence: Similar Rates of Neural Tube Defects Among Deliveries Regardless of Maternal HIV Status and Dolutegravir Exposure in Hospital Birth Surveillance in Eswatini". Open Forum Infectious Diseases. 10 (9) ofad441. doi:10.1093/ofid/ofad441. PMC 10502921. PMID 37720700.
  19. ↑ "What to Start: Initial Antiretroviral Regimens During Pregnancy for People Who Are Antiretroviral-Naïve". Clinicalinfo. 17 September 2021. Retrieved 25 August 2026.
  20. ↑ "Appendix C: Antiretroviral Counseling Guide for Health Care Providers". Clinicalinfo. 12 June 2025. Retrieved 25 August 2026.
  21. ↑ "GSK wins priority status for new HIV drug in U.S." Retrieved 25 August 2026.
  22. ↑ "Drug Approval Package: Tivicay (dolutegravir) Tablets NDA #204790". U.S. Food and Drug Administration (FDA). 13 September 2013. Archived from the original on 15 February 2016. Retrieved 12 June 2020.
  23. ↑ "ViiV Healthcare receives approval for Tivicay (dolutegravir) in Canada for the treatment of HIV" (Press release). ViiV Healthcare. 4 November 2013. Retrieved 25 August 2026 – via PR Newswire.
  24. ↑ "ViiV Healthcare announces US FDA approval of the first-ever dispersible tablet formulation of dolutegravir, Tivicay PD, a once-daily treatment for children living with HIV". GSK (Press release). Retrieved 12 June 2020.
  25. ↑ Silverman E (25 April 2024). "Colombia issues a compulsory license for an HIV medicine and 'plants a flag for global health equity'". STAT. Retrieved 28 July 2024.
  26. ↑ "Colombia Issues Compulsory License To Enable It To Access Generic HIV Drug, Dolutegravir - Health Policy Watch". 25 April 2024. Retrieved 28 July 2024.
  27. ↑ "More than 100 low- and middle-income countries have now received the WHO-recommended treatment for HIV thanks to access-oriented voluntary licensing agreements - MPP". Retrieved 28 July 2024.
  28. ↑ "UNAIDS welcomes new decision in Colombia allowing more affordable access to quality HIV medicines" (Press release). UNAIDS. 4 October 2023. Retrieved 28 July 2024.
  29. ↑ "ViiV Healthcare statement on compulsory licence for dolutegravir in Colombia". ViiV Healthcare (Press release). Retrieved 28 July 2024.
  30. ↑ "Dolutegravir - Paediatrics (DTG)". Medicines Patent Pool. Retrieved 28 July 2024.
  31. ↑ Shetty D (15 July 2024). "World's Leading HIV Drug Reduces Carbon Emissions by 26 Million Tons In Comparison to Predecessor" (Press release). Health Policy Watch.
  32. ↑ "New Unitaid report: World's leading HIV drug proven to have reduced global CO2 emissions by 26 million tons" (Press release). UNITAID. 15 July 2024.