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Pharmacy Practice in Focus: Health Systems
As HIV treatment and prevention evolve, the use of long-acting injectables and their role in combating the HIV epidemic grows.
Long-acting injectables (LAIs) are a relatively newer option for HIV treatment and prevention. Although injectable regimens may not be preferable to all patients due to fear of needles or limited transportation to the clinic, some people living with HIV (PLWH) may prefer infrequent injections rather than daily oral medications. Reasons for preferring LAIs can include challenges with adherence to oral medications or with stigma related to having these medications in their home. For patients facing these challenges, LAIs may significantly improve quality of life. Further, data continue to be published in different patient populations, showing that these injectable therapies remain safe and efficacious in a variety of patients.
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LA cabotegravir/rilpivirine (LA CAB/RPV; Cabenuva; ViiV Healthcare) has been FDA approved since January 2021 as a complete regimen for the treatment of HIV in patients who are virologically suppressed. It can be administered either every 4 or every 8 weeks intramuscularly by a health care professional (HCP) and does not require an oral lead-in period. Outside of patients who are virologically suppressed, more recent data have emerged supporting its use in patients unable to achieve or maintain viral suppression on oral antiretroviral therapy (ART).
In a demonstration project done by the Ward 86 HIV clinic in San Francisco, California, 57 patients with viremia were started on LA CAB/RPV.1 Among this cohort, 54 patients (95%) achieved virologic suppression by a median of 33 days. Of note, 1 patient did not achieve suppression until after their fifth injection, and 1 patient required the addition of lenacapavir (LEN; Sunlenca; Gilead Sciences, Inc) to achieve viral suppression. In a smaller study from the University of Mississippi Medical Center in Jackson, 12 patients with persistent viremia were started on LA CAB/RPV.2 All patients achieved viral suppression within 3 months of starting therapy.
Additionally, a model-based analysis using a simulated cohort of patients similar to that of the Ward 86 clinic showed that LA CAB/RPV had substantial improvements in viral suppression, engagement in care, and survival over 3 years and beyond, with greatest benefit in patients with lower CD4 counts at therapy initiation.3 A commonality in these studies was that LA CAB/RPV was coupled with significant case management/social services, multidisciplinary support, and close follow-up.
Based on this growing body of data, the US Department of Health and Human Services HIV/AIDS guidelines and the International Antiviral Society (IAS)–USA HIV treatment guidelines were recently updated to recommend use of LA CAB/RPV on a case-by-case basis in select patients with persistent virologic failure who are unable to take oral ART despite intensive adherence counseling, who do not have evidence of resistance to CAB or RPV, and who have high risk for disease progression (CD4 count < 200/μL or history of AIDS-defining complications). Additionally, the IAS–USA HIV treatment guidelines recommend that patients be included in shared decision-making with their HCP, with intensive follow-up and case management services available.4,5 If virologic response is inadequate, the guidelines recommend drug resistance testing.
LA CAB (Apretude; ViiV Healthcare) was approved as HIV preexposure prophylaxis (PrEP) in December 2021. It is administered intramuscularly by an HCP every 8 weeks and does not require an oral lead-in period. Its approval was based on the phase 2b/3 HPTN 083 study (NCT02720094), showing that LA CAB was superior to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC; Truvada; Gilead Sciences, Inc) for PrEP in cisgender men and transgender women.6 A subsequent study, HPTN 084 (NCT03164564), showed that LA CAB was also superior to TDF/FTC in women.7 Additional substudies have been done from both HPTN 083 and 084 that further support the use of LA CAB.
In a follow-up analysis of HPTN 083, investigators looked at the efficacy rate of LA CAB after the first year of unblinded therapy and found that LA CAB maintained its superior efficacy compared with TDF/FTC, with a 65% reduction in incidence of HIV infection.8 In a subanalysis of HPTN 084 in pregnant women, which was presented at the 25th International AIDS Conference (AIDS 2024), LA CAB was shown to be safe and well tolerated, supporting the use and/or continuation of LA CAB in this population.9 There were also no apparent negative effects of LA CAB on infant outcomes.
LEN is the newest antiretroviral and is a first-in-class capsid inhibitor, which was FDA approved in December 2022.10 Not only does LEN represent a novel mechanism of action to treat HIV, but it is also the longest-acting injectable ART currently on the market.
After a short oral lead-in period, LEN is administered subcutaneously by an HCP every 6 months, which may provide a significant advantage to PLWH who struggle with daily medication adherence or have difficulty with more frequent transportation to the clinic. Its current labeled indication shows it is to be used in combination with other antiretroviral agents in heavily treatment-experienced adults with multidrug-resistant (MDR) HIV-1 infection after failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations; this indication is based on the results of the CAPELLA trial (NCT04150068).11
There are now several ongoing studies that may expand the use of LEN beyond treatment for patients with MDR HIV. For example, CALIBRATE (NCT04143594) was a phase 2 trial that showed the potential use of LEN in treatment-naive patients, indicating that a phase 3 study in this population may be conducted in the future.12
At the 2024 Conference on Retroviruses and Opportunistic Infections, there was a case series presented of PLWH (n = 34) who were placed on an injectable-only treatment regimen (CAB +/– RPV plus LEN). The patients in this series demonstrated resistance to RPV but faced significant social challenges and adherence issues with oral ART. Although this regimen is not FDA approved, 94% of the patients in this series achieved virologic suppression on this regimen.13 This series supports more research into injectable-only CAB/LEN regimens for PLWH with resistance who are unable to take standard oral medications.
A topic of interest for LEN in 2024 seemed to be related to its use as PrEP. There are 5 phase 3 trials (the PURPOSE trials) ongoing for LEN in PrEP for different patient populations. The PURPOSE 1 trial (NCT04994509) results brought a standing ovation at AIDS 2024, as the findings demonstrated 100% efficacy and 0 cases of HIV when LEN was used for PrEP in high-risk cisgender African women (n = 2134) vs 16 cases on oral TDF/FTC and 39 cases on tenofovir alafenamide fumarate/FTC.14 The results of PURPOSE 1 were simultaneously published in the New England Journal of Medicine.
The results of the PURPOSE 2 trial (NCT04925752) were published at the end of November 2024.15 PURPOSE 2 explores PrEP in cisgender men, transgender women, transgender men, and gender nonbinary individuals and includes patients from the US, Argentina, Brazil, Mexico, Peru, Puerto Rico, South Africa, and Thailand. LEN had 99.9% efficacy in preventing HIV in this population, with only 2 incident cases in the LEN group (n = 2179).16
PURPOSE 3 will evaluate PrEP for cisgender women in the US, and PURPOSE 4 will evaluate PrEP among persons who inject drugs in the US. PURPOSE 5 is now enrolling patients interested in PrEP in the UK and France.
Of note, LEN currently comes with a high cost in the US, at an estimated $15,600 per dose and approximately $42,000 for the first year, including the oral lead-in. This significant financial burden makes it essential for pharmacists to assist with evaluating a patient’s insurance and connecting them with Gilead patient assistance programs (PAPs).17 In some good news, however, Gilead recently signed royalty-free voluntary licensing agreements to generic manufacturers in 120 low- and lower–middle income countries to support low-cost access in high-incidence, low-resource countries.
Allison Field, PharmD, BCIDP, AAHIVP, is a clinical pharmacy specialist in infectious diseases at ECU Health Medical Center in Greenville, North Carolina.
Melissa George, PharmD, BCIDP, is a clinical pharmacy specialist in infectious diseases at ECU Health Medical Center in Greenville, North Carolina.
Pharmacists who care for PLWH and patients interested in PrEP should remain informed about the emerging uses for CAB/RPV, CAB, and LEN to support optimizing ART regimens with these injectable options for a patient’s lifestyle and financial feasibility. Utilizing these regimens is typically most successful with a multidisciplinary approach, specifically with pharmacists assessing for drug interactions, as well as providing support for navigating PAPs and candid patient counseling that emphasizes the importance of coming to injection appointments to avoid increasing drug resistance.
The authors have nothing to disclose.
