The future of long-acting agents for preexposure prophylaxis
- PMID: 35762373
- PMCID: PMC9467455
- DOI: 10.1097/COH.0000000000000735
The future of long-acting agents for preexposure prophylaxis
Abstract
Purpose of review: The main reason for the failure of oral preexposure prophylaxis (PrEP) regimens for HIV is poor adherence. Intramuscular cabotegravir was recently approved for PrEP, and a number of other long-acting antiretroviral formulations and products are currently in clinical development. This includes subcutaneous and intravenous injections, implants, and microarray (microneedle) patches, as well as extended duration oral drugs. The success and future uptake of these products will depend on a variety of factors.
Recent findings: Long-acting delivery of antiretroviral agents for PrEP confers significant advantages over short-acting oral delivery. This is exemplified by the superior efficacy of intramuscular cabotegravir given every eight weeks as compared to daily oral co-formulated tenofovir disoproxil fumarate and emtricitabine. There is also evidence for PrEP efficacy for a broadly neutralizing monoclonal antibody given intravenously every eight weeks. One of the leading candidates for long-acting PrEP, islatravir, was being studied as a monthly oral drug or a nonerodable subcutaneous implant inserted for up to 12 months. However, clinical studies of this agent were put on hold in late 2021 because of unanticipated lymphopenia.
Summary: Long-acting antiretroviral products have substantial promise for PrEP and have particular advantages over daily oral drugs based mainly on improved adherence. However, there are barriers to further uptake that include the need for more intensive interaction with systems of healthcare delivery, greater expense and complexity of implementation, and unexpected long-term toxicities.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Conflict of interest statement
Conflicts of interest
C.F. reports serving as a paid consultant for Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories, and ViiV Healthcare.
Similar articles
-
Cabotegravir Extended-Release Injectable Suspension: A Review in HIV-1 Pre-Exposure Prophylaxis.Drugs. 2022 Sep;82(14):1489-1498. doi: 10.1007/s40265-022-01791-3. Epub 2022 Oct 18. Drugs. 2022. PMID: 36255686 Review.
-
How could HIV-1 drug resistance impact preexposure prophylaxis for HIV prevention?Curr Opin HIV AIDS. 2022 Jul 1;17(4):213-221. doi: 10.1097/COH.0000000000000746. Curr Opin HIV AIDS. 2022. PMID: 35762376 Free PMC article. Review.
-
Preexposure Prophylaxis for the Prevention of HIV Infection: Evidence Report and Systematic Review for the US Preventive Services Task Force.JAMA. 2019 Jun 11;321(22):2214-2230. doi: 10.1001/jama.2019.2591. JAMA. 2019. PMID: 31184746
-
Pre-exposure prophylaxis to prevent HIV infection: current status, future opportunities and challenges.Drugs. 2015 Feb;75(3):243-51. doi: 10.1007/s40265-015-0355-4. Drugs. 2015. PMID: 25673022 Free PMC article. Review.
-
Challenges and Opportunities for Preexposure Prophylaxis.Top Antivir Med. 2021 Oct-Nov;29(4):399-406. Top Antivir Med. 2021. PMID: 34856093 Free PMC article.
Cited by
-
Gay and Bisexual Men's Perceptions about a Potential HIV Vaccine within a Post-COVID-19 Era: A Qualitative Study.AIDS Behav. 2024 Aug 10. doi: 10.1007/s10461-024-04450-8. Online ahead of print. AIDS Behav. 2024. PMID: 39122906
-
Combating antimicrobial resistance in malaria, HIV and tuberculosis.Nat Rev Drug Discov. 2024 Jun;23(6):461-479. doi: 10.1038/s41573-024-00933-4. Epub 2024 May 15. Nat Rev Drug Discov. 2024. PMID: 38750260 Review.
-
Broadly neutralizing antibodies for HIV prevention: a comprehensive review and future perspectives.Clin Microbiol Rev. 2024 Jun 13;37(2):e0015222. doi: 10.1128/cmr.00152-22. Epub 2024 Apr 30. Clin Microbiol Rev. 2024. PMID: 38687039 Review.
-
Weekly Oral Tenofovir Alafenamide Protects Macaques from Vaginal and Rectal Simian HIV Infection.Pharmaceutics. 2024 Mar 11;16(3):384. doi: 10.3390/pharmaceutics16030384. Pharmaceutics. 2024. PMID: 38543278 Free PMC article.
-
What does the scale-up of long-acting HIV pre-exposure prophylaxis mean for the global hepatitis B epidemic?J Int AIDS Soc. 2024 Mar;27(3):e26218. doi: 10.1002/jia2.26218. J Int AIDS Soc. 2024. PMID: 38444112 Free PMC article.
References
-
-
Landovitz RJ, Donnell D, Clement ME, Hanscom B, Cottle L, Coelho L, 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.
**This is the first large randomized trial to demonstrate the superiority of injectable cabotegravir PrEP over a standard one-pill once-a-day regimen.
-
-
-
Flexner C, Owen A, Siccardi M, Swindells S. Long-acting drugs and formulations for the treatment and prevention of HIV. Int J Antimicrob Agents 2021. Jan;57(1):106220. doi: 10.1016/j.ijantimicag.2020.106220.
**This is a recent comprehensive review of long-acting drug delivery technologies in development for HIV.
-
-
- Nachman S, Townsend CL, Abrams EJ, Archary M, Capparelli E, Clayden P, et al. Long acting/extended release antiretroviral products for HIV treatment and prevention in infants, children, adolescents and pregnant and breastfeeding women: knowledge gaps and research priorities. Lancet HIV 2019; 2019. Aug; 6: e552–e558. doi: 10.1016/S2352-3018(19)30147-X. - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous