The impact of long-acting injectables (LAIs) for HIV was discussed at the 35th European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global conference in Vienna, Austria.
Historically, managing HIV has required a lifelong commitment to daily oral antiretroviral therapy (ART). These regimens often involve multiple drugs from different classes, such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and integrase strand transfer inhibitors (INSTIs), necessitating strict adherence to daily dosing schedules. To simplify treatment and improve adherence, fixed-dose combination (FDC) pills are now commonly used, consolidating multiple active pharmaceutical ingredients (APIs) into a single tablet.
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Common examples include Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide), Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide), and Complera (rilpivirine/emtricitabine/tenofovir disoproxil fumarate). While these single-tablet regimens reduced pill burden, challenges have persisted, particularly for individuals with complex health needs or those experiencing side effects from specific drug components.
The HIV treatment landscape has further evolved with the introduction of LAI therapies, offering alternatives to daily oral regimens. Cabenuva, combining cabotegravir and rilpivirine, is the first complete LAI regimen approved for virologically suppressed individuals, administered monthly or every two months. Sunlenca (lenacapavir), a first-in-class capsid inhibitor, is approved for heavily treatment-experienced patients with multidrug-resistant HIV, administered twice yearly in combination with other antiretrovirals. Apretude (cabotegravir) is the first LAI approved for HIV pre-exposure prophylaxis (PrEP), administered every two months to reduce the risk of sexually acquired HIV infection in high-risk adults and adolescents. These LAI options represent a significant shift in HIV care, potentially enhancing adherence, reducing stigma, and improving quality of life for individuals living with or at risk of HIV. Yet, while the clinical data is compelling, the real-world success of the LAIs hinges not just on the pharmacology but on political movements, health equity, and thoughtful implementation.
LAIs offer more than convenience. They present a meaningful solution to persistent adherence challenges, particularly to people facing housing instability, substance use, mental illness, or stigma. For many, taking a daily pill is not just a medical task but a daily reminder of an incurable diagnosis. “You wouldn’t believe how many people are hiding, even at home or at work, when they have to take pills,” said Dr. Pedro Cahn during the session. Long-acting options offer dignity, discretion, and psychological relief. In a global patient survey cited in the session, over 40% of respondents listed long-acting medicines as their top priority.
Clinical trials such as FLAIR, ATLAS, and ATLAS-2M have shown that switching virologically suppressed patients from daily oral ART to LAIs cabotegravir and rilpivirine (CAB/RPV) can maintain viral control with high satisfaction. The CARES study (Kenya, Uganda, South Africa) confirmed success in lower-income settings, while the IMPACT 2017 trial showed 100% suppression in adolescents. However, these trials often exclude the very populations who stand to benefit most—those who are not virally suppressed at baseline.
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By GlobalDataThat is where real-world innovation is breaking ground. Ward 86, a clinic in San Francisco, is one of the few settings where long-acting CAB/RPV is being used in viremic, high-risk individuals. “We said you do not have to be virologically suppressed—just come in every 4–8 weeks,” explained Dr. Monica Gandhi. Their demonstration project includes over 430 patients, with many showing remarkable improvements despite housing insecurity, mental health struggles, or substance abuse. This approach challenges current guidelines and shows that LAIs could be more than a maintenance therapy—they could be an entry point to care.
Yet, access remains a critical issue. Across most high-income countries, regulatory approvals have outpaced reimbursement. Ironically, in the US, it is often low-income patients on Medicaid who can access LAIs more easily than those with private insurance. “It’s actually low-income people who can get long-acting cabotegravir,” Gandhi noted, flipping the typical narrative around affordability.
From a global perspective, long-acting options risk becoming yet another innovation that worsens inequality unless health systems proactively plan for equitable rollout. Unless countries adopt equity-focused policies—such as differentiated care models, flexible dosing, and patent reform—LAIs may remain out of reach for millions.
Key opinion leaders (KOLs) previously interviewed by GlobalData have praised the emergence of LAIs for improving patient freedom, privacy, and reducing daily burden of pill-taking. However, they also cited concerns around their integration into routine care. In particular, KOLs noted that frequent clinic visits, administration logistics, and scheduling challenges are seen as significant barriers, particularly in already overstretched healthcare systems. Despite strong clinical interest, implementation has been a challenge, reflecting the need to align clinical workflows and infrastructure with new treatment models such as longer dosing intervals and simplified delivery, which may be needed to fully realise their potential.
Another under-discussed barrier is the drug–drug interaction between rilpivirine and rifampin, a first-line tuberculosis (TB) treatment. In regions with high co-infection rates, this contraindication severely limits LAI feasibility. Treating TB without rifampin is not a viable option, raising the need for alternative regimens or second-generation injectables that can work in tandem.
The future is promising. Innovations such as lenacapavir—a capsid inhibitor with six-month dosing—could further simplify care, particularly for prevention. But with resistance concerns and limited access outside high-income settings, careful surveillance and real-world data will be key.
LAIs are not just a medical breakthrough—they are a litmus test for global health equity. If rolled out with intentionality, they could dramatically reshape HIV care, especially for the most marginalised. But without access, they risk deepening the very disparities they aim to solve. Ministries of health, global funders, and pharma must work together to ensure that this next chapter in HIV treatment is one of inclusion, not exclusion.
