Long-Acting Injectables for the Prevention or Treatment of HIV

In recent years, long acting injectables (LAIs) have been introduced into clinical practice for the treatment and prevention of Human Immunodeficiency Virus (HIV) infection. These agents present another option for patients who may struggle with adherence to a daily oral medication, have difficulties swallowing oral medications, and those who generally prefer a long-acting agent. There are currently two LAIs approved for the treatment of HIV: cabotegravir co-packaged with rilpivirine (CAB/RPV) and lenacapavir (LEN). CAB/RPV was FDA approved in 2021 and is a complete regimen for the treatment of HIV-1 infection.¹ It is administered as two gluteal intramuscular injections either every four or eight weeks. Lenacapavir is a first-in-class capsid inhibitor and was FDA approved in 2022 for use in heavily-treatment experienced adults with multidrug resistant HIV-1 infection in combination with other antiretrovirals.² Lenacapavir is administered as two subcutaneous injections into the abdomen every 6 months, and at initiation patients must also take oral tablets based on 1 of 2 dosing strategies.

There is currently one LAI approved for HIV pre-exposure prophylaxis (PrEP). Cabotegravir (CAB) was FDA approved in 2021 and is administered as a gluteal intramuscular injection every 8 weeks.³ In addition to those LAIs currently approved for the treatment and prevention of HIV, there are several long-acting agents currently under investigation, including new dosing strategies for currently available agents, weekly oral regimens, and monoclonal antibodies. Notably, results were recently published regarding the use of subcutaneous LEN given every six months for PrEP.⁴ Tables 1 and 2 below include information regarding trials supporting the use of LAIs for the treatment and prevention of HIV.

Summary

Implementation of LAIs in the clinic setting requires a robust multidisciplinary approach, including providers, nurses, pharmacists, social workers, case managers, and support staff. Before initiating LAIs, patients should be thoroughly evaluated for drug interactions, history of drug resistance, hepatitis B infection, and willingness to regularly attend clinic visits. Additionally, patients should be counseled on the importance of receiving medication doses on time to avoid the development of drug resistance or loss of protection against HIV acquisition. Once initiated, LAIs may significantly improve medication adherence by avoiding the need for a daily oral tablet, increase patient satisfaction, and improve patient outcomes. A number of organizations have resources online to assist clinics interested in utilizing LAIs, including the American Academy of HIV Medicine (AAHIVM) which has a Long-Acting Agent Resource Center.¹²

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References

1. Cabenuva (cabotegravir and rilpivirine) [prescribing information]. Durham, NC: GlaxoSmithKline; December 2023.

2. Sunlenca (lenacapavir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; September 2023.

3. Apretude (cabotegravir) [prescribing information]. Durham, NC: ViiV Healthcare; December 2023.

4. Bekker LG, Das M, Abdool Karim Q, et al. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. N Engl J Med. Published online July 24, 2024.

5. Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression. N Engl J Med. 2020;382(12):1112-1123.

6. Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet. 2021;396(10267):1994-2005.

7. Orkin C, Arasteh K, Górgolas Hernández-Mora M, et al. Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection. N Engl J Med. 2020;382(12):1124-1135.

8. Segal-Maurer S, DeJesus E, Stellbrink HJ, et al. Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection. N Engl J Med. 2022;386(19):1793-1803.

9. 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.

10. 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):1779-1789.

11. Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection (PURPOSE 2). ClinicalTrials.gov identifier: NCT04925752. Updated July 12, 2024. Accessed August 27, 2024. https://clinicaltrials.gov/study/NCT04925752

12. Long-acting agent resource center. American Academy of HIV Medicine. Accessed September 4, 2024. https://hivlaa.org/