Long-Acting HIV Treatments: Advances in ART & PrEP | Healio News

The landscape of HIV prevention and treatment is undergoing a significant shift, moving beyond daily oral medications to long-acting options. These advancements offer the potential to reduce dosing frequency, minimize reminders of an HIV diagnosis, and address challenges related to adherence—a persistent hurdle for many living with or at risk of HIV. Several long-acting agents have recently become available, transforming both treatment and prevention strategies.

A Latest Era in HIV Management

Historically, antiretroviral therapy (ART) involved complex regimens with substantial daily pill burdens. Today, ART typically consists of a single, once-daily pill, dramatically improving tolerability and convenience. However, adherence remains a critical factor. Individuals may struggle with daily medication due to pill fatigue, mental health concerns, substance use, unstable housing, or the stigma associated with taking daily pills. Long-acting ART (LA-ART) aims to overcome these obstacles by reducing the frequency of dosing and, the visible reminders of HIV status.

Studies have demonstrated that LA-ART can improve viral suppression among individuals with adherence difficulties. Long-acting regimens have proven superior to daily oral medications in preventing HIV infection among high-risk populations, offering benefits such as increased patient acceptance and fewer adherence issues.

Cabotegravir/Rilpivirine (Cabenuva)

Cabenuva, a combination of cabotegravir and rilpivirine, represents a novel LA-ART regimen for HIV-1 treatment. Approved by the FDA for adolescents and adults weighing at least 35 kg, Cabenuva requires patients to be virologically suppressed with no prior treatment failure or drug resistance. It’s administered via intramuscular injection, with dosing options including monthly or every-two-month schedules.

• Monthly Dosing: CAB 600 mg + RPV 900 mg on the last day of current treatment, or with an oral lead-in period.
• Every 2-Month Dosing: CAB 600 mg + RPV 900 mg repeated one month apart for initial doses.

Maintenance dosing follows, with monthly injections of CAB 400 mg + RPV 600 mg or, for the two-month schedule, CAB 600 mg + RPV 900 mg starting two months after the last initiation dose. An optional 28-day oral lead-in allows for tolerability assessment before initiating injections, and oral tablets can cover missed injection appointments for up to two months.

Clinical trials have shown high rates of viral suppression with Cabenuva, and real-world observational studies confirm these findings, even among individuals facing adherence challenges and complex social or medical needs. However, injection site reactions, such as pain, swelling, and nodules, are common, though generally mild to moderate and resolving within days. Other reported adverse effects include fever, fatigue, headache, increased creatinine phosphokinase, liver toxicity, and hypersensitivity reactions. Patients should be monitored for at least 10 minutes post-injection for potential reactions. The FDA initially approved this regimen in 2021.

Cabotegravir (Apretude) for PrEP

In 2021, cabotegravir alone received FDA approval as Apretude, the first long-acting injectable for pre-exposure prophylaxis (PrEP). Approved for adults and adolescents weighing at least 35 kg, it has demonstrated superior protection compared to daily oral tenofovir disoproxil fumarate-emtricitabine (FTC/TDF) in preventing HIV infection, particularly among cisgender men who have sex with men and transgender women who have sex with men. A meta-analysis revealed a 79% reduction in HIV infection risk with cabotegravir compared to daily oral PrEP.

The regimen involves an initial oral lead-in dose of 30 mg daily for approximately one month to assess tolerability, followed by 600 mg intramuscularly once a month for two consecutive months. Maintenance dosing consists of 600 mg IM every two months. As with Cabenuva, adverse effects are similar.

Lenacapavir (Sunlenca)

Sunlenca, a first-in-class HIV capsid inhibitor, received FDA approval in 2022 for treating multi-drug-resistant HIV-1 in heavily treatment-experienced adults with limited options, and more recently as PrEP. It is not used as a standalone treatment and must be combined with an optimized background regimen. Lenacapavir is available as both an oral tablet and a subcutaneous injection.

Treatment and PrEP dosing involves administering both 600 mg oral tablet and 927 mg subcutaneous injection on day 1, followed by another 600 mg oral dose on day 2. For treatment only, additional oral doses are given on day 8, followed by a 927 mg SQ injection on day 15. Maintenance dosing consists of 927 mg SQ injections every 26 weeks.

Clinical trials, such as CAPELLA, have shown high rates of viral suppression even in patients with limited treatment options. The PURPOSE-1 and PURPOSE-2 trials demonstrated exceptional efficacy for PrEP, with zero HIV infections among cisgender women in PURPOSE-1 and a 96% reduction in risk in PURPOSE-2 compared to daily oral TDF-FTC. Common side effects include injection site reactions.

Ibalizumab (Trogarzo)

Trogarzo was the first FDA-approved HIV medication not requiring daily dosing, approved in 2018. It’s a humanized IgG4 monoclonal antibody that prevents HIV-1 entry without immunosuppression. Approved for adults with multidrug-resistant HIV-1 who have failed other regimens, it’s administered as a 2,000 mg IV loading dose followed by 800 mg IV infusions every two weeks.

Looking Ahead

The future of LA-ART is promising, with several medications in development. While current agents are administered via injection, oral options are being explored. A once-weekly combination of islatravir and ulonivirine showed promise but was halted due to lymphocyte reductions. Another weekly oral combination, lenacapavir and islatravir, is also under development. If approved, a once-weekly oral regimen could significantly improve convenience and adherence.

Jeff Brock, PharmD, MBA, BCIDP, is a Healio | Infectious Disease News Editorial Board Member and infectious disease pharmacy specialist at MercyOne Medical Center in Des Moines, Iowa. He can be reached at [email protected].