By: Ranier Simons, ADAP Blog Guest Contributor
Benjamin Franklin is credited with the phrase ‘an ounce of prevention is worth a pound of cure.’ In other words, it is better to prevent something than to deal with the consequences or attempt to fix the damage after the fact. This sentiment can be applied to many aspects of the human condition, including public health, in general, and specifically HIV/AIDS. That is why developments in Pre-Exposure Prophylaxis (PrEP) are so valuable. Recently, researchers reported a new milestone in clinical trials involving the long-acting injectable antiretroviral lenacapavir as an option for PrEP. It could be a game-changer for HIV prevention, if potential patients can access it.
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| Photo Source: European AIDS Treatment Group |
The FDA approved Gilead Science’s lenacapavir, under the brand name Sunlenca, in December 2022 as an HIV treatment for adults with limited treatment options because of things such as multi-drug resistance.[1] Sunlenca is administered as a twice-yearly injection that is given in conjunction with combinations of other HIV antiretrovirals. Gilead has continued developing additional utilizations of lenacapavir, with clinical trials exploring its efficacy as a pre-exposure prophylaxis option. This month, Gilead released interim results from one of those studies that are so promising it will begin to start seeking global regulatory approval towards the end of the year.[2]
The recent successful clinical trial results came from the Phase III PURPOSE 2 study. This study involved 2,180 subjects who were cisgender men, transgender men, transgender women, and gender non-binary individuals who have sex with partners assigned male at birth.[2] The study compared twice-yearly injections of lenacapavir to taking a once-daily Truvada pill. There were only two cases of HIV infection among the 2,180 subjects, meaning 99.9% of those in the lenacapavir arm did not acquire HIV. The comparative arm consisted of 1,087 people who take a daily Truvada pill. That group contained nine subjects who contracted HIV.[3] The study proved that twice-yearly lenacapavir performed better than the current standard form of PrEP in daily Truvada. Compared to Truvada, researchers reported that lenacapavir reduced the likelihood of contracting HIV by 96% as compared to no intervention.[3]
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| Photo Source: Amfar |
These findings support lenacapavir’s effectiveness, as proven by Gilead’s Phase III PURPOSE 1 Study. The PURPOSE 1 clinical trial involved over 5,300 cisgender adolescent girls and young women ages 16-26 in South Africa and Uganda.[4] This trial also compared twice-yearly injected lenacapavir to daily oral Truvada (emitricitabine/ tenofovir disoproxil fumarate) or daily oral Descovy (emitricitabine/tenofovir alafenamide). The efficacy of lenacapavir was 100%, with none of those receiving lenacapavir contracting HIV. Conversely, 16 of the 1,068 women who took Truvada and 39 of the 2,136 women who received Descovy contracted HIV.[4]
Long-acting injectables for PrEP create a prevention option offering more ease of use than daily pills, thus increasing uptake and consistency.[5] Studies have shown that some people have adherence challenges regarding taking daily medication. For some, keeping up with a daily regimen is too psychologically or logistically taxing. For others, like some of the women in countries in Africa, having their medication discovered could pose personal safety issues. Moreover, various access challenges, including transportation, have an affect on successfully utilizing daily treatments for PrEP. A twice-yearly injection helps maintain privacy, reducing stigma, and requires less of a burden on the frequency of physical access to clinics. Moreover, it is easier to get patient buy-in on a twice-yearly injection compared to adherence to a daily treatment to prevent a disease they do not have.
Lenacapavir as PrEP would also be an injectable PrEP alternative to Apretude (cabotegravir). Presently, cabotegravir is an FDA-approved long-acting injectable for PrEP that is administered bi-monthly. However, in the two years since its approval in the U.S., there have only been about 11,000 prescriptions given compared to the roughly 382,000 annual users of oral PrEP.[6] That is only about 1.4% of PrEP users. Additionally, lenacapavir is administered subcutaneously in the abdominal area, unlike cabotegravir, which is a deep intra-muscular injection. A subcutaneous injection may be more appealing to some than a deep intra-muscular injection. Furthermore, a subcutaneous injection could mean easier access for administration since it requires less expertise than a deep intra-muscular injection.
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| Photo Source: Daily Caring |
The innovation of long-acting injectable PrEP is lost if those who are most in need cannot access it. Thus, financial innovation needs to occur as well. Long-acting injectable PrEP will most likely cost significantly more than the current generic version of Truvada as daily PrEP in pill form, which can be obtained for about $20 a month.[3] Insurers will need to be convinced of the benefits of covering twice-yearly injectable lenacapavir. Most importantly, Medicaid, which provides care for over 40% of adults under the age of 65 living with HIV, will need to effectively cover long-acting injectable PrEP.[7] Data shows that PrEP uptake is lower among those on Medicaid compared to people with private insurance, with privately insured people initiating PrEP at a seven times higher rate.[7]
The O’Neill Institute for National and Global Health Law released a publication suggesting how Medicaid can ensure coverage for long-acting injectables. The two overarching ideas are that the federal government facilitates support for long-acting integration and states modify practices to effect widespread long-acting injectable access.[8] On the federal level, the institute suggests that the Centers for Medicare and Medicaid Services (CMS) issue guidance on Medicaid’s role in supporting PrEP uptake and update their 2016 Informational Bulletin on HIV Prevention and Care Delivery to include all currently available HIV therapies and services. Additionally, they point out there is no senior administrator in CMS with HIV expertise focused on coordinating HIV policy with Medicare and Medicaid regarding the National HIV/AIDS Strategy. Thus, they should appoint an official to handle that task.[8] On a state level, they suggest that states should examine their Medicaid managed care contract standards to ensure all covered HIV medications are available across all health plans.[8]
Ongoing inquiries provide data showing that patients have favorable inclinations toward long-acting injectables, especially once they become fully aware of what is available. One source of this data is a project executed by ADAP Advocacy entitled ‘HIV LONG-ACTING INJECTABLES: Patient Access Considerations for Injectable HIV Therapies & Injectable HIV Pre-Exposure Prophylaxis’. The project consisted of a quantitative survey, a qualitative focus group, and an analysis of data among those who were HIV-positive in terms of long-acting injectables for treatment and those who were HIV-negative regarding long-acting injectables for prevention.
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The sample population focused on long-acting injectables for prevention included participants from 35 states, the District of Columbia and Puerto Rico.[9] Of these respondents, the majority reported that they would prefer provider or self-administered long-acting injectable PrEP as opposed to daily oral pills.[9] There was a mixture of awareness of the specific medication, Apretude. However, upon being made aware of it, those who were already aware and those newly aware were mostly open to learning more about using it or would strongly consider switching from a pill-based regimen.[9] A frequent concern was being unsure if they would be able to afford it or worried if their insurance would cover it.[9]
The PURPOSE 1 and 2 clinical trials and ongoing data indicate the promise of effective prevention that long-acting injectables can bring. Future results from PURPOSE 3, 4, and 5 will continue to strengthen proof of efficacy among even more diverse groups. It is imperative that education, policy, funding, and infrastructure be created and maintained to ensure access to those who are most in need of and desire to utilize not only long-acting injectable PrEP, but long-acting HIV treatment of all forms.
[1] Mahobe, R. (2022, December 22). U.S. FDA approves Gilead's long-acting HIV drug Sunlenca. Retrieved from https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-approves-gileads-long-acting-hiv-drug-sunlenca-2022-12-22/#:~:text=By%20Raghav%20Mahobe,Licensing%20Rights%20%2C%20opens%20new%20tab
[2] Manalac, T. (2024, September 13). Gilead touts 96% HIV risk reduction with twice-Yearly PrEP, eyes regulatory filings. Retrieved from https://www.biospace.com/drug-development/gilead-touts-96-hiv-risk-reduction-with-twice-yearly-prep-eyes-regulatory-filings
[3] Mundell, E. (2024, September 13). Twice-yearly injection cuts HIV risk by 96%, but will cost cut access? Retrieved from https://medicalxpress.com/news/2024-09-yearly-hiv-access.html#google_vignette
[4] Foster, Robin. (2024, June 24). Twice-a-year injection gives women full protection against HIV, trial finds. Retrieved from https://www.healthday.com/health-news/infectious-disease/twice-a-year-injection-gives-women-full-protection-against-hiv-trial-finds
[5] Edwards, G. G., Miyashita-Ochoa, A., Castillo, E. G., Goodman-Meza, D., Kalofonos, I., Landovitz, R. J., Leibowitz, A. A., Pulsipher, C., El Sayed, E., Shoptaw, S., Shover, C. L., Tabajonda, M., Yang, Y. S., & Harawa, N. T. (2023). Long-Acting Injectable Therapy for People with HIV: Looking Ahead with Lessons from Psychiatry and Addiction Medicine. AIDS and Behavior, 27(1), 10–24. https://doi.org/10.1007/s10461-022-03817-z
[6] Cairns, G. (2024, March 29). Why is the roll-out of injectable PrEP taking so long?. Retrieved from https://www.aidsmap.com/news/mar-2024/why-roll-out-injectable-prep-taking-so-long
[7] Wirth, D., Crowley, J. (2024, Sept 19). Medicaid must prepare to cover twice-yearly HIV prevention injection. Retrieved from https://www.statnews.com/2024/09/19/medicaid-prep-long-lasting-twice-yearly-prep-hiv-injection-cms/
[8] O'Neill Institute. (2024, July). Medicaid Leadership Must Ensure Access to Longer-Acting HIV Products. Retrieved from https://oneill.law.georgetown.edu/wp-content/uploads/2024/07/ONL_BIIB_Medicaid_Leadership_P5.pdf
[9] ADAP Advocacy. (2024, June). Patient access considerations for Injectable HIV Therapies & Injectable HIV Pre-exposure prophylaxis. Retrieved from https://www.adapadvocacy.org/pdf-docs/2024_ADAP_Project_Long_Acting_Injectables_Final_Report_06-25-24.pdf
Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.
