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Cabotegravir Extended-Release Injectable Suspension: A Review in HIV-1 Pre-Exposure Prophylaxis

Drugs volume 82, pages 1489–1498 (2022)Cite this article

Abstract

Cabotegravir extended-release (ER) injectable suspension (Apretude™) is the first long-acting injectable option to be approved for HIV-1 pre-exposure prophylaxis (PrEP). As an HIV-1 integrase strand transfer inhibitor, cabotegravir ER injectable suspension prevents DNA integration and inhibits HIV-1 replication. Its slow absorption and long elimination half-life permit infrequent dosing (1 month apart for two consecutive months, and every 2 months thereafter). Cabotegravir ER injectable suspension is indicated in the USA for PrEP to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents weighing ≥ 35 kg who have a negative HIV-1 test prior to initiation. In clinical trials, cabotegravir ER injectable suspension had superior efficacy to oral daily emtricitabine/tenofovir disoproxil fumarate (DF) in preventing acquisition of HIV-1 in at-risk transgender women (TGW), cisgender men who have sex with men (MSM), and cisgender women. The drug was generally well tolerated, although further long-term data are needed to fully determine its safety. With its convenient, less-frequent dosing schedule and its long-acting formulation enabling intramuscular administration, cabotegravir ER injectable suspension represents a novel and efficacious alternative to daily oral PrEP.

Plain Language Summary

Despite major advances in the prevention of HIV-1 transmission, there remain barriers to the widespread effective use of pre-exposure prophylaxis (PrEP). Approved daily oral PrEP requires people who do not have HIV-1 to take a pill every day to protect them from acquiring the infection. The availability of long-acting injectable PrEP that does not require daily dosing has the potential to improve uptake and adherence, particularly in high-risk individuals. Cabotegravir extended-release (ER) injectable suspension is the first long-acting injectable option to be approved for PrEP, and is given as an intramuscular injection as few as six times per year. Cabotegravir ER injectable suspension is more effective than daily oral emtricitabine/tenofovir disoproxil fumarate for preventing HIV-1 infection in adults who are at risk of sexually acquiring HIV-1. Cabotegravir ER injectable suspension is generally well tolerated and offers a convenient alternative to daily oral PrEP.

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References

  1. World Health Organization. HIV/AIDS. 2021. https://www.who.int/news-room/fact-sheets/detail/hiv-aids. Accessed 20 Sep 2022.

  2. Pilgrim NA, Evans TM, Czarnogorski M. A layer plus approach to implementation research and collaboration for long-acting injectable pre-exposure prophylaxis for HIV prevention. Health Promot Pract. 2022. https://doi.org/10.1177/15248399211053584.

    Article  PubMed  Google Scholar 

  3. Durham SH, Milam A, Waer D, et al. Cabotegravir: the first long-acting injectable for HIV preexposure prophylaxis. Ann Pharmacother. 2022. https://doi.org/10.1177/10600280221102532.

    Article  PubMed  Google Scholar 

  4. Clement ME, Kofron R, Landovitz RJ. Long-acting injectable cabotegravir for the prevention of HIV infection. Curr Opin HIV AIDS. 2020;15(1):19–26.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Flexner C. The future of long-acting agents for preexposure prophylaxis. Curr Opin HIV AIDS. 2022;17(4):192–8.

    Article  CAS  PubMed  Google Scholar 

  6. Spinelli MA, Grinsztejn B, Landovitz RJ. Promises and challenges: cabotegravir for preexposure prophylaxis. Curr Opin HIV AIDS. 2022;17(4):186–91.

    Article  CAS  PubMed  Google Scholar 

  7. ViiV Healthcare. APRETUDE (cabotegravir extended-release injectable suspension), for intramuscular use: US prescribing information. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215499s000lbl.pdf. Accessed 20 Sep 2022.

  8. Markham A. Cabotegravir plus rilpivirine: first approval. Drugs. 2020;80(9):915–22.

    Article  CAS  PubMed  Google Scholar 

  9. Smith RA, Wu VH, Zavala CG, et al. In vitro antiviral activity of cabotegravir against HIV-2. Antimicrob Agents Chemother. 2018;62(10):e01299-e1318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Andrews CD, Yueh YL, Spreen WR, et al. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge. Sci Transl Med. 2015;7(270):270ra4.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Vishwanathan SA, Zhao C, Luthra R, et al. Sexually transmitted infections and depot medroxyprogesterone acetate do not impact protection from simian HIV acquisition by long-acting cabotegravir in macaques. AIDS. 2022;36(2):169–76.

    Article  CAS  PubMed  Google Scholar 

  12. Dobard C, Makarova N, Nishiura K, et al. Long-acting cabotegravir protects macaques against repeated penile simian-human immunodeficiency virus exposures. J Infect Dis. 2020;222(3):391–5.

    Article  CAS  PubMed  Google Scholar 

  13. Andrews CD, Spreen WR, Mohri H, et al. Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus. Science. 2014;343(6175):1151–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Andrews CD, Bernard LS, Poon AY, et al. Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251. AIDS. 2017;31(4):461–7.

    Article  CAS  PubMed  Google Scholar 

  15. Yoshinaga T, Seki T, Miki S, et al. Novel secondary mutations C56S and G149A confer resistance to HIV-1 integrase strand transfer inhibitors. Antiviral Res. 2018;152:1–9.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Delany-Moretlwe S, Hughes JP, Bock P, et al. Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial. Lancet. 2022;399(10337):1779–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Smith SJ, Zhao XZ, Burke TR Jr, et al. Efficacies of cabotegravir and bictegravir against drug-resistant HIV-1 integrase mutants. Retrovirology. 2018;15(1):37.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Han K, Wannamaker P, Lu H, et al. Safety, tolerability, pharmacokinetics, and acceptability of oral and long-acting cabotegravir in HIV-negative Chinese men. Antimicrob Agents Chemother. 2022;66(3):e0205721.

    Article  PubMed  Google Scholar 

  20. Landovitz RJ, Li S, Eron JJ Jr, et al. Tail-phase safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected adults: a secondary analysis of the HPTN 077 trial. Lancet HIV. 2020;7(7):e472–81.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Yu Y, Bigos KL, Marzinke MA, et al. A population pharmacokinetic model based on HPTN 077 of long-acting injectable cabotegravir for HIV PrEP. Br J Clin Pharmacol. 2022;88(10):4623–32.

    Article  CAS  PubMed  Google Scholar 

  22. 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):e331–40.

    Article  PubMed  Google Scholar 

  23. 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): e1002690.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Marzinke MA, Grinsztejn B, Fogel JM, et al. Characterization of human immunodeficiency virus (HIV) infection in cisgender men and transgender women who have sex with men receiving injectable cabotegravir for HIV prevention: HPTN 083. J Infect Dis. 2021;224(9):1581–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Grinsztejn B, Hanscom B, Wang Z, et al. Transgender women (TGW) in HPTN 083: an evaluation of safety, efficacy, and gender affirming hormonal therapy (GAHT) interactions with long-acting cabotegravir (CAB-LA) [abstract no. 12707 plus poster]. In: The 24th International AIDS Conference. 2022.

  26. Landovitz RJ, Donnell D, Tran H, et al. Updated efficacy, safety, and case studies in HPTN 083: CAB-LA vs TDF/FTC for PrEP [abstract no. 96]. In: Conference on Retroviruses and Opportunistic Infections. 2022.

  27. Psaros C, Landovitz RJ, Rice W, et al. Understanding participant experiences and preferences in an injectable PrEP trial: a qualitative sub-study of barriers, facilitators and preferences for PrEP use among MSM and TGW [abstract no. OALC0503]. J Int AIDS Soc. 2021;24(Suppl 4):30.

    Google Scholar 

  28. Eshleman SH, Fogel JM, Piwowar-Manning E, et al. Characterization of human immunodeficiency virus (HIV) infections in women who received injectable cabotegravir or tenofovir disoproxil fumarate/emtricitabine for HIV prevention: HPTN 084. J Infect Dis. 2022;225(10):1741–9.

    Article  CAS  PubMed  Google Scholar 

  29. Delany-Moretlwe S, Hughes JP, Bock P, et al. Long acting cabotegravir: updated efficacy and safety results from HPTN 084 [abstract no. 13063]. In: The 24th International AIDS Conference. 2022.

  30. Tolley E, Bula A, Chitukuta M, et al. Acceptability of injectable cabotegravir versus daily oral TDF/FTC for PrEP: lesson from HPTN 084 [abstract no. 8961 plus poster]. In: The 24th International AIDS Conference. 2022.

  31. US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States: 2021 update. 2021. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf. Accessed 20 Sep 2022.

  32. Celum C, Baeten J. PrEP for HIV prevention: evidence, global scale-up, and emerging options. Cell Host Microbe. 2020;27(4):502–6.

    Article  CAS  PubMed  Google Scholar 

  33. Sugarman J, Donnell DJ, Hanscom B, et al. Ethical issues in establishing the efficacy and safety of long-acting injectable pre-exposure prophylaxis for HIV prevention: the HPTN 083 trial. Lancet HIV. 2021;8(11):e723–8.

    Article  PubMed  Google Scholar 

  34. US National Institutes of Health. ClinicalTrials identifier NCT04692077. 2020. https://clinicaltrials.gov. Accessed 20 Sep 2022.

  35. US National Institutes of Health. ClinicalTrials identifier NCT04824131. 2021. https://clinicaltrials.gov. Accessed 20 Sep 2022.

  36. Meyers K, Rodriguez K, Brill AL, et al. Lessons for patient education around long-acting injectable PrEP: findings from a mixed-method study of phase II trial participants. AIDS Behav. 2018;22(4):1209–16.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Levy ME, Agopian A, Magnus M, et al. Is long-acting injectable cabotegravir likely to expand PrEP coverage among MSM in the District of Columbia? J Acquir Immune Defic Syndr. 2021;86(3):e80–2.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Irie WC, Calabrese SK, Patel RR, et al. Preferences for HIV preexposure prophylaxis products among Black women in the U.S. AIDS Behav. 2022;26(7):2212–23.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Cohen MS, Landovitz RJ. Assessing the role of long-acting cabotegravir preexposure prophylaxis of human immunodeficiency virus: opportunities and aspirations. J Infect Dis. 2021;223(1):1–3.

    Article  CAS  PubMed  Google Scholar 

  40. Schmidt HA, Rodolph M, Schaefer R, et al. Long-acting injectable cabotegravir: implementation science needed to advance this additional HIV prevention choice. J Int AIDS Soc. 2022;25(7): e25963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wray TB, Chan PA, Klausner JD, et al. Gay, bisexual, and other men who have sex with men who are not on oral PrEP may be less interested in available injectable products than in oral PrEP: examining individual-level determinants of interest and barriers across products. AIDS Behav. 2022. https://doi.org/10.1007/s10461-022-03708-3.

    Article  PubMed  Google Scholar 

  42. Rael CT, Lopez-Ríos J, McKenna SA, et al. Transgender women’s barriers, facilitators, and preferences on tailored injection delivery strategies to administer long-acting injectable cabotegravir (CAB-LA) for HIV pre-exposure prophylaxis (PrEP). AIDS Behav. 2021;25(12):4180–92.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Rael CT, Martinez M, Giguere R, et al. Transgender women’s concerns and preferences on potential future long-acting biomedical HIV prevention strategies: the case of injections and implanted medication delivery devices (IMDDs). AIDS Behav. 2020;24(5):1452–62.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Conniff J, Evensen A. Preexposure prophylaxis (PrEP) for HIV prevention: the primary care perspective. J Am Board Fam Med. 2016;29(1):143–51.

    Article  PubMed  Google Scholar 

  45. Sharfstein JM, Killelea A, Dangerfield D. Long-acting cabotegravir for HIV prevention: issues of access, cost, and equity. JAMA. 2022;327(10):921–2.

    Article  CAS  PubMed  Google Scholar 

  46. Jamieson L, Johnson LF. The relative cost-effectiveness of long-acting injectable cabotegravir versus oral pre-exposure prophylaxis: a modelled economic evaluation and threshold analysis in South Africa based on the HPTN 083 and 084 trials. Lancet. 2022. https://doi.org/10.2139/ssrn.4047136.

    Article  Google Scholar 

  47. Joob B, Wiwanikit V. Changing from tenofovir/emtricitabine to cabotegravir for pre exposure prophylaxis for HIV in men who have sex with men: a cost utility analysis from an endemic country. J Assoc Physicians India. 2022;70(2):11–2.

    PubMed  Google Scholar 

  48. Neilan AM, Landovitz RJ, Le MH, et al. Cost-effectiveness of long-acting injectable HIV preexposure prophylaxis in the United States: a cost-effectiveness analysis. Ann Intern Med. 2022;175(4):479–89.

    Article  PubMed  Google Scholar 

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Acknowledgements

During the peer review process, the manufacturer of cabotegravir ER injectable suspension was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Hannah A. Blair

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Hannah Blair is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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The manuscript was reviewed by: C. Flexner, Departments of Medicine, Pharmacology & International Health, Johns Hopkins University, Baltimore, MD, USA; K. Scarsi, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA; E. D. Weld, Infectious Diseases & Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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Blair, H.A. Cabotegravir Extended-Release Injectable Suspension: A Review in HIV-1 Pre-Exposure Prophylaxis. Drugs 82, 1489–1498 (2022). https://doi.org/10.1007/s40265-022-01791-3

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