Barriers to Uptake of Long-Acting Antiretroviral Products for Treatment and Prevention of Human Immunodeficiency Virus (HIV) in High-Income Countries

Stanley E Cooper, Joshua Rosenblatt, Roy M Gulick, Stanley E Cooper, Joshua Rosenblatt, Roy M Gulick

Abstract

Long-acting injectable antiretroviral therapy (LAI-ART) for the treatment and prevention of human immunodeficiency virus (HIV) holds great potential to shift treatment paradigms by offering an alternative to daily oral medication. However, significant challenges at the drug, patient, and system levels risk impeding the uptake and implementation of LAI-ART. This review aims to describe the known and anticipated barriers to uptake of LAI-ART in high-income countries, as well as the ongoing research addressing some of these barriers to improve the delivery and uptake of LAI-ART products.

Keywords: HIV-1; antiretroviral therapy; cabotegravir; long-acting injectable antiretroviral; preexposure prophylaxis; rilpivirine.

Conflict of interest statement

Potential conflicts of interest. S. E. C. reports research training funding from the National Institutes of Health (NIH) through grant number T32AI007613. R. G. reports research funding from an NIH UM1 grant for HIV clinical trials; royalty payments from Elsevier for a textbook chapter on HIV therapy; and payments for educational talks at academic and non-profit institutions. J. R. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

References

    1. CDC . Ending HIV transmission-test, treat, and prevent, 2019. Available at:. Accessed 15 March 2022.
    1. Martin M, Del Cacho E, Codina C, et al. . Relationship between adherence level, type of the antiretroviral regimen, and plasma HIV type 1 RNA viral load: a prospective cohort study. AIDS Res Hum Retroviruses 2008; 24:1263–8.
    1. 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; 382:1112–23.
    1. Swindells S, Lutz T, Van Zyl L, et al. . Week 96 extension results of a phase 3 study evaluating long-acting cabotegravir with rilpivirine for HIV-1 treatment. AIDS 2022; 36:185–94.
    1. 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; 382:1124–35.
    1. Orkin C, Oka S, Philibert P, et al. . Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV 2021; 8:e185–96.
    1. 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, noninferiority study. Lancet 2020; 396:1994–2005.
    1. Jaeger H, Overton ET, Richmond G, et al. . Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 96-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet HIV 2021; 8:e679–89.
    1. Landovitz RJ, Donnell D, Clement ME, et al. . Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med 2021; 385:595–608.
    1. 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; 399:1779–89.
    1. EMA . Rekambys European Medicines Agency prescribing information, 2020. Available at: . Accessed 10 April 2022.
    1. EMA . Vocabria European Medicines Agency prescribing information, 2021. . Accessed 10 April 2022.
    1. FDA . Cabenuva (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension), co-packaged for intramuscular use, 2021. Available at: . Accessed 31 March 2022.
    1. FDA . Apretude (cabotegravir extended-release injectable suspension), for intramuscular use, 2021. Available at: . Accessed 6 February 2022.
    1. Orkin C, Bernal Morell E, Tan DHS, et al. . Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study. Lancet HIV 2021; 8:e668–78.
    1. Rizzardini G, Overton ET, Orkin C, et al. . Long-acting injectable cabotegravir and rilpivirine for HIV maintenance therapy: week 48 pooled analysis of phase 3 ATLAS and FLAIR trials. J Acquir Immune Defic Syndr 2020; 85:498–506.
    1. Landovitz RJ, Li S, Jr EJ, 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:e472–81.
    1. Cutrell AG, Schapiro JM, Perno CF, et al. . Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis. AIDS 2021; 35:1333–42.
    1. Centers for Disease Control and Prevention . Diagnoses of HIV infection in the United States and dependent areas, 2018 (updated). HIV Surveil Rep. 2020; 31:1–119. Available at: . Accessed 31 March 2022.
    1. Song R, Hall HI, Green TA, et al. . Using CD4 data to estimate HIV incidence, prevalence, and percent of undiagnosed infections in the United States. J Acquir Immune Defic Syndr 2017; 74:3–9.
    1. Philbin MM, Parish C, Kinnard EN, et al. . Interest in long-acting injectable pre-exposure prophylaxis (LAI PrEP) among women in the women's Interagency HIV study (WIHS): a qualitative study across six cities in the United States. AIDS Behav 2021; 25:667–78.
    1. Centers for Disease Control and Prevention . Estimated HIV Incidence and Prevalence in the United States, 2014–2018. HIV Surveill Suppl Rep. 2020; 25:1–77. Available at: . Accessed 31 March 2022.
    1. Shrestha R, DiDomizio EE, Kim RS, Altice FL, Wickersham JA, Copenhaver MM. Awareness about and willingness to use long-acting injectable pre-exposure prophylaxis (LAI-PrEP) among people who use drugs. J Subst Abuse Treat 2020; 117:108058.
    1. Weld ED, Rana MS, Dallas RH, et al. . Interest of youth living with HIV in long-acting antiretrovirals. J Acquir Immune Defic Syndr 2019; 80:190–7.
    1. Macapagal K, Nery-Hurwit M, Matson M, Crosby S, Greene GJ. Perspectives on and preferences for on-demand and long-acting PrEP among sexual and gender minority adolescents assigned male at birth. Sex Res Social Policy 2021; 18:39–53.
    1. Delany-Moretlwe S, Hughes J, Xu G, et al. . Adolescent and parent experiences with long-acting injectables in the MOCHA study. [CROI 2022 abstract 739]. In special issue: abstracts from the 2022 Conference on Retroviruses and Opportunistic Infections. Top Antivir Med 2022; 30:295.
    1. Goedel WC, Nunn AS, Chan PA, et al. . A shot at equity? Addressing disparities among black MSM in the coming era of long-acting injectable preexposure prophylaxis. AIDS 2019; 33:2110–2.
    1. Suite DH, La Bril R, Primm A, Harrison-Ross P. Beyond misdiagnosis, misunderstanding and mistrust: relevance of the historical perspective in the medical and mental health treatment of people of color. J Natl Med Assoc 2007; 99:879–85.
    1. Huang YA, Zhu W, Smith DK, Harris N, Hoover KW. HIV Preexposure prophylaxis, by race and ethnicity—United States, 2014–2016. MMWR Morb Mortal Wkly Rep 2018; 67:1147–50.
    1. Olansky E, Mansergh G, Pitts N, et al. . PrEP awareness in the context of HIV/AIDS conspiracy beliefs among Black/African American and Hispanic/Latino MSM in three urban US cities. J Homosex 2020; 67:833–43.
    1. Philbin MM, Parish CL, Kinnard EN, et al. . Multisite study of women living with HIV's perceived barriers to, and interest in, long-acting injectable antiretroviral therapy. J Acquir Immune Defic Syndr 2020; 84:263–70.
    1. Beckham SW, Sanchez TM, Zlotorzynska M, et al. . Preferences for implementing long-acting injectable pre-exposure prophylaxis among cisgender men who have sex with men in the United States. J Int AIDS Soc 2021; 24:29–31.
    1. Sevelius JM, Deutsch MB, Grant R. The future of PrEP among transgender women: the critical role of gender affirmation in research and clinical practices. J Int AIDS Soc 2016; 19:21105.
    1. 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; 24:1452–62.
    1. 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; 25:4180–92.
    1. Delany-Moretlwe S, Hughes J, Xu G, et al. . Evaluation of CAB-LA safety and PK in pregnant women in the blinded phase of HPTN 084. [CROI 2022 abstract 700]. In special issue: abstracts from the 2022 Conference on Retroviruses and Opportunistic Infections. Top Antivir Med 2022; 30:278.
    1. Jolayemi O, Bogart LM, Storholm ED, et al. . Perspectives on preparing for long-acting injectable treatment for HIV among consumer, clinical and nonclinical stakeholders: a qualitative study exploring the anticipated challenges and opportunities for implementation in Los Angeles County. PLoS One 2022; 17:e0262926.
    1. Panel on Antiretroviral Guidelines for Adults and Adolescents . Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. Available at:. Accessed 24 Feb 2022.
    1. CDC . Preexposure prophylaxis for the prevention of HIV infection in the United States—2021 update. Available at:. Accessed 25 February 2022.
    1. Murray MI, 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; 19:129–38.
    1. Marcus JL, Killelea A, Krakower DS. Perverse incentives—HIV prevention and the 340B drug pricing program. N Engl J Med 2022; 386:2064–6.
    1. Collins LF, Collins LF, Corbin-Johnson D, et al. . 887. Implementation of long-acting injectable cabotegravir/rilpivirine for HIV-1 treatment at a Ryan White-funded clinic in the U.S. South. Open Forum Infect Dis 2021; 8:S535.
    1. Czarnogorski M, Garris G, D’Amico R, et al. . Customize: overall results from a hybrid III implementation-effectiveness study examining implementation of cabotegravir and rilpivirine long-acting injectable for HIV treatment in US healthcare settings; final patient and provider data. Presented at: 11th International AIDS Society Conference on HIV Science; July 18–21, 2021; virtual. Accessed 31 January 2021.
    1. Gutner C, Dakhia S, Gill M, et al. . Cabotegravir and rilpivirine implementation study in European locations (CARISEL): examining healthcare staff attitudes during a hybrid III implementation-effectiveness trial implementing cabotegravir + rilpivirine long-acting injectable (CAB + RPV LA) for people living with HIV. Presented at: 18th European AIDS Conference; October 27–30, 2021; virtual & United Kingdom. Accessed 24 February 2022.

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