Drug information

Audio
Pronounce:
Other Names:
CAB, CAB LA, cabotegravir LA, cabotegravir sodium, cabotegravir long-acting injectable, cabotegravir extended-release injectable suspension
Drug Class:
Integrase Strand Transfer Inhibitor (INSTIs)
Molecular Formula:

C19 H17 F2 N3 O5

Registry Number:
1051375-10-0 (CAS)
Chemical Name:

(3S,11aR)-N-((2,4-difluorophenyl)methyl)-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo(3,2-a)pyrido(1,2-d)pyrazine-8-carboxamide

Chemical Class:
Carbamoyl pyridone
Organization:
ViiV Healthcare
Phase of Development:

Cabotegravir is in Phase 3 development for HIV prevention. On May 4, 2021, the manufacturers of cabotegravir announced that they have begun a rolling submission of a New Drug Application (NDA) with the US Food and Drug Administration (FDA) for approval of long-acting, injectable cabotegravir for HIV prevention.

FDA-approved Products for HIV Treatment: Cabenuva, a two-drug regimen consisting of cabotegravir and rilpivirine extended-release injectable suspensions is FDA-approved for HIV treatment. Additionally, an oral tablet formulation of cabotegravir (brand name: Vocabria) is FDA-approved for use with oral rilpivirine for short-term HIV treatment.

 
What is cabotegravir?What is cabotegravir?

What is cabotegravir?

 

Cabotegravir is a drug that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV. It is approved as part of a long-acting injectable two-drug regimen with rilpivirine under the brand name Cabenuva. Cabotegravir is also approved as an oral tablet under the brand name Vocabria for use with oral rilpivirine (brand name: Edurant).5,6 Additionally, cabotegravir is currently being studied as an investigational drug to prevent HIV infection.3

Cabotegravir belongs to a group of HIV drugs called integrase inhibitors.7 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.

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

Which clinical trials are studying cabotegravir?Which clinical trials are studying cabotegravir?

Select clinical trials of cabotegravir

 

Cabotegravir for HIV Prevention

Study Names: ECLAIR; NCT02076178
Phase: 2a
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety, tolerability, and acceptability of cabotegravir LA for pre-exposure prophylaxis (PrEP).
Selected Study Results: Results published in the journals Lancet HIV and HIV Clinical Trials indicated that cabotegravir LA was generally safe and well tolerated. Side effects of moderate intensity or greater were more common with cabotegravir LA than placebo, mainly due to injection-site pain. The majority of these injection-site pain events were mild-to-moderate in intensity.8–10 

Study Names: HPTN 077; NCT02178800
Phase: 2a
Status: This study has been completed.
Locations: United States, Brazil, Malawi, South Africa
Purpose: The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of cabotegravir LA in participants without HIV.
Selected Study Results: Results were published in PLOS Medicine and showed that injection site reactions of moderate intensity or greater were more common with cabotegravir LA than placebo. Most injection site reactions were related to pain and were mild to moderate in severity.11,12

Study Names: HPTN 083; NCT02720094
Phase: 2b/3
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Argentina, Brazil, Peru, South Africa, Thailand, Vietnam
Purpose: The purpose of this study is to compare the safety and effectiveness of cabotegravir LA to oral emtricitabine/tenofovir disoproxil fumarate (Truvada) for PrEP in cisgender men and transgender women who have sex with men.
Selected Study Results: Results published in the New England Journal of Medicine showed that cabotegravir LA given every 8 weeks is superior to daily oral Truvada in preventing HIV infection among cisgender men and transgender women who have sex with men. Side effects of moderate intensity or greater occurred in a similar proportion of participants in each study group. Injection site reactions, mostly mild or moderate in intensity, were common with cabotegravir LA.13,14

Study Names: HPTN 083-01 (a sub-study of HPTN 083); NCT04692077
Phase: 2
Status: This study is currently recruiting participants.
Location: United States
Purpose: The purpose of this study is to evaluate the safety and acceptability of cabotegravir LA in adolescent males.15

Study Names: HPTN 084; NCT03164564
Phase: 3
Status: This study is currently recruiting participants.
Locations: Botswana, Kenya, Malawi, South Africa, Swaziland, Uganda, Zimbabwe
Purpose: The purpose of this study is to compare the safety and effectiveness of cabotegravir LA to oral Truvada for PrEP in women.
Selected Study Results: Results presented at HIVR4P 2021 indicated that cabotegravir LA given every 8 weeks is superior to daily oral Truvada in preventing HIV infection among cisgender women. With the exception of injection site reactions, there were few differences between study groups when looking at side effects of moderate intensity or greater.3,16

Study Names: HPTN 084-01 (a sub-study of HPTN 084); NCT04824131
Phase: 2
Status: This study is currently recruiting participants.
Locations: South Africa, Uganda, Zimbabwe 
Purpose: The purpose of this study is to evaluate the safety and acceptability of cabotegravir LA in adolescent females.17

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

What side effects might cabotegravir cause?What side effects might cabotegravir cause?

What side effects might cabotegravir 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 cabotegravir listed above.

ECLAIR (NCT02076178):

During the oral therapy part of the ECLAIR study, treatment-related side effects were mostly mild to moderate. No serious side effects were reported with oral cabotegravir.10

The majority of participants receiving cabotegravir LA had an injection site reaction. Most of these reactions were mild to moderate in intensity and most were cases of injection-site pain. Among the participants receiving cabotegravir LA, 19% had a serious injection site reaction and four participants withdrew from the study because of injection intolerability. Other injection site reactions reported by participants receiving cabotegravir LA included mild itchiness, nodules/bumps, warmth to the touch, bruising, and hardened tissue.10

HPTN 077 (NCT02178800):

In the HPTN 077 study, ten participants discontinued cabotegravir because of drug-related side effects, including gastrointestinal problems, rash, and neurologic issues. Serious side effects reported by participants taking cabotegravir included vertigo and weakness.18

During the injection phase of the study, the majority of participants receiving cabotegravir LA had side effects that were moderate or higher in intensity. Injection site reactions, most of which were mild to moderate, were common in participants receiving cabotegravir LA. Only one participant discontinued cabotegravir due to an injection site reaction. Two participants receiving cabotegravir LA had a severe injection site reaction, although neither participant stopped cabotegravir LA injections.18

HPTN 083 (NCT02720094):

In the HPTN 083 trial, there were no notable safety concerns reported. The percentage of participants having serious side effects or side effects of moderate intensity or higher was similar between both the cabotegravir and Truvada groups. The majority of participants receiving cabotegravir LA (approximately 81%) experienced injection site reactions. Most of these reactions were mild or moderate, occurred less frequently over time, and were related to pain or tenderness. Only 2.4% of participants receiving cabotegravir LA stopped treatment because of an injection-related side effect.14

HPTN 084 (NCT03164564):

In the HTPN 084 trial, only 32% of the participants receiving cabotegravir LA experienced injection site reactions, Most of these reactions were mild, related to pain, and generally occurred more frequently with the first injection, compared with later injections. No participants stopped treatment because of an injection-related side effect.3,16

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

Additional information on side effects known to be associated with cabotegravir can be found in the FDA-approved Full Prescribing Information for Cabenuva and Vocabria.5,6

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

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

 

More information about cabotegravir-related research studies is available from ClinicalTrials.gov.

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.

ReferencesReferences

References

 

  1. United States National Library of Medicine. ChemIDplus Advanced: cabotegravir. https://chem.nlm.nih.gov/chemidplus/rn/1051375-10-0. Accessed August 13, 2021
  2. Whitfield T, Torkington A, van Halsema C. Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date. HIVAIDS Auckl NZ. 2016;8:157-164.
  3. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 3 double blind safety and efficacy study of long-acting injectable cabotegravir compared to daily oral TDF/FTC for pre-exposure prophylaxis in HIV-uninfected women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 22, 2017. NLM Identifier: NCT03164564. https://clinicaltrials.gov/ct2/show/NCT03164564. Accessed August 13, 2021
  4. ViiV Healthcare: Press release, dated May 4, 2021. ViiV Healthcare initiates rolling submission of new drug application with US FDA for long-acting cabotegravir for prevention of HIV. https://viivhealthcare.com/en-us/us-news/us-articles/2021/viiv-healthcare-initiates-rolling/. Accessed August 13, 2021
  5. ViiV Healthcare Company: Cabenuva: full prescribing information, January 2021. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1698baf3-f895-4c42-a1b1-e9ee3f20da36. Accessed August 13, 2021
  6. ViiV Healthcare Company. Vocabria: full prescribing information, January 2021. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=66d450fb-cca4-476c-b0c7-c0730e3e4cf3. Accessed August 13, 2021
  7. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed August 13, 2021
  8. ViiV Healthcare. A Phase IIa study to evaluate the safety, tolerability and acceptability of long acting injections of the HIV integrase inhibitor, GSK1265744, in HIV uninfected men (ECLAIR). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 27, 2014. NLM Identifier: NCT02076178. https://clinicaltrials.gov/ct2/show/NCT02076178. Accessed August 13, 2021
  9. Markowitz M, Frank I, Grant RM, et al. Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial. Lancet HIV. 2017;4(8):e331-e340.
  10. Murray M, Markowitz M, Frank I, et al. Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial. HIV Clin Trials. 2018;19:1-10. doi:10.1080/15284336.2018.1511346
  11. National Institute of Allergy and Infectious Diseases (NIAID). A Phase IIa study to evaluate the safety, tolerability and pharmacokinetics of the investigational injectable HIV integrase inhibitor, GSK1265744, in HIV-uninfected men and women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 27, 2014. NLM Identifier: NCT02178800. https://clinicaltrials.gov/ct2/show/NCT02178800. Accessed August 13, 2021
  12. Landovitz RJ, Li S, Grinsztejn B, et al. Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a Phase 2a randomized controlled trial. PLoS Med. 2018;15(11). doi:10.1371/journal.pmed.1002690
  13. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 2b/3 double blind safety and efficacy study of injectable cabotegravir compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), for pre-exposure prophylaxis in HIV-uninfected cisgender men and transgender women who have sex with men. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 21, 2016. NLM Identifier: NCT02720094. https://clinicaltrials.gov/ct2/show/NCT02720094. Accessed August 13, 2021
  14. Landovitz RJ, Donnell D, Clement ME, et al. Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med. 2021;385(7):595-608. doi:10.1056/NEJMoa2101016
  15. National Institute of Allergy and Infectious Diseases (NIAID). Safety, tolerability and acceptability of long-acting cabotegravir (CAB LA) for the prevention of HIV among adolescent males - a sub-study of HPTN 083. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 6, 2021. NLM Identifier: NCT04692077. https://www.clinicaltrials.gov/ct2/show/NCT04692077. Accessed August 13, 2021
  16. Delany-Moretlwe S, Hughes JP, Bock P, et al. Long acting injectable cabotegravir is safe and effective in preventing HIV infection in cisgender women: results from HPTN 084. HIV Research for Prevention (HIVR4P); January 27-28 and February 3-4, 2021. Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2021. https://www.natap.org/2021/HIVR4P/HIVR4P_11.htm. Accessed August 13, 2021
  17. National Institute of Allergy and Infectious Diseases (NIAID). Safety, tolerability and acceptability of long-acting cabotegravir (CAB LA) for the prevention of HIV among adolescent females - a sub-study of HPTN 084. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 22, 2020. NLM Identifier: NCT04824131. https://www.clinicaltrials.gov/ct2/show/NCT04824131. Accessed August 13, 2021
  18. Landovitz R, Li S, Grinsztejn B, et al. Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected women and men HPTN 077. Slides presented at: International AIDS Society (IAS) Conference on HIV Science; July 23-26, 2017; Paris, France. http://programme.ias2017.org/PAGMaterial/PPT/2899_91/IAS2017_Landovitz_Final_072417.pptx. Accessed August 13, 2021
 

Last Reviewed: August 13, 2021