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LA ART
Advancing Long-Acting Treatment and Prevention for HIV: Opportunities and Challenges

Released: April 25, 2025

Expiration: April 24, 2026

Darcy Wooten
Darcy Wooten, MD, MS
Activity Information

Activity

Progress
1
Course Completed
Key Takeaways
  • Long-acting (LA) antiretroviral (ART) adoption and integration are hampered by structural, financial, and logistical barriers.
  • Expanding LA ART access will require a multifaceted approach to address barriers at the clinical, individual, and systemic level.  

Long-acting (LA) antiretroviral therapy (ART) represents a transformative advancement in the management and prevention of HIV, offering the potential to enhance adherence and reduce transmission rates. However, despite its promise, widespread LA ART implementation in the United States remains hindered by systemic, logistical, and socioeconomic barriers. 

Benefits of LA ART
Conventional ART requires daily oral administration, which may present significant challenges for some people. This may lead to inconsistent adherence, and consequently, suboptimal treatment outcomes. LA ART, such as bimonthly injectable cabotegravir (CAB)/rilpivirine (RPV), mitigates the burden of daily medication intake, fostering improved adherence and sustained viral suppression. Of note, both observational and controlled studies have demonstrated the significant benefit of LA ART vs daily oral ART among people living with HIV who face adherence challenges.

Beyond clinical efficacy, LA ART is also associated with high levels of patient satisfaction. LA ART can minimize stigma-related psychological burdens and enhance quality of life since it reduces medication administration frequency, and for some people living with HIV, it alleviates the daily reminder of having the virus.

Similar benefits were observed with LA injectable pre-exposure prophylaxis (PrEP), offering an effective alternative for people struggling with adherence to daily oral PrEP. In clinical trials, including HPTN 083 and HPTN 084, LA CAB was significantly more effective in preventing HIV acquisition compared with daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). I think this is likely because of better adherence with LA CAB: In these 2 studies, most participants who acquired HIV while receiving oral ART demonstrated low or nonadherence. Likewise, LA injectable lenacapavir also demonstrated superior efficacy in HIV prevention compared with traditional oral PrEP. 

Despite these benefits, adoption and integration of LA ART into routine clinical practice are hampered by multifaceted barriers at structural, financial, and logistical levels.

  • Financial and administrative hurdles: Cost remains a major impediment, with insurance coverage and reimbursement policies often limiting access. Many insurers require prior authorization, which can delay or restrict access to this therapy. In healthcare settings with limited administrative capacity to navigate these processes, LA ART usage is likely to remain suboptimal.
  • Limited availability in clinical settings: Currently, LA ART must be administered by healthcare professionals, restricting its availability to select clinical settings. Most primary-care and noninfectious diseases specialty clinics do not stock or administer these medications. As a result, people living with HIV often need to visit HIV specialty clinics every 2 months for injections, a significant barrier for those who lack reliable transportation, live in rural areas, or have inflexible work or caregiving responsibilities.
  • Healthcare system constraints: LA ART administration requires time, trained personnel, and modifications to clinical workflows. Many healthcare facilities, already operating at full capacity, struggle to allocate the necessary resources for integrating LA ART into their services. Addressing these logistical challenges will be critical for broader implementation.
  • Awareness and eligibility limitations: Many people living with HIV remain unaware of LA ART as a treatment or prevention option, limiting uptake. In addition, some people living with HIV may not be eligible for LA ART because of preexisting resistance mutations or contraindications to injectable CAB/RPV.

Strategies to Bridge the Gap
Expanding LA ART access requires a multipronged approach that addresses financial, logistical, and systemic challenges.

  • Insurance and policy reforms: Broadening insurance coverage and streamlining reimbursement processes would significantly enhance access, particularly in nonspecialty-care settings.
  • Decentralized delivery models: Establishing community-based administration sites, particularly in places where affected communities are already accessing care, such as pharmacies and mobile clinics, would increase accessibility. Future innovations enabling self-administration of LA ART could further reduce access barriers. 
  • Additional LA ART options: Developing and licensing additional LA ART agents are also needed to provide more options for people living with HIV who have resistance mutations to CAB and/or RPV. In addition, the development of LA ART with a high genetic barrier to resistance should be prioritized to decrease the chance that resistance develops if virologic failure occurs.
  • Healthcare professional training and integration into primary care: Education and training programs for healthcare professionals are essential for seamless integration into routine care. Incorporating LA ART for PrEP into primary-care settings is particularly crucial, given the shortage of infectious disease and HIV specialists in regions with high HIV incidence.
  • Community engagement and education: Public awareness campaigns involving community leaders and targeting disproportionately affected communities can address stigma, dispel misconceptions, foster trust, and promote LA ART uptake.
  • Addressing social determinants of health: At the core of improving LA ART access lies the imperative to address broader social determinants of health. Stigma, structural racism, housing insecurity, and socioeconomic disparities remain formidable barriers to equitable HIV care and prevention. Without meaningful efforts to dismantle these systemic inequities, even the most effective biomedical innovations will fail to reach those who need them most.

Prioritizing these strategies, we can work toward ensuring that LA ART fulfills its potential as a powerful tool in the fight against HIV by reducing transmission and improving health outcomes for vulnerable populations.

We will discuss this topic further in a series of free, live sessions at academic medical centers across the United States. To request one of these free, CME-certified, expert-led sessions at your academic medical center, click here.

Your Thoughts
What LA ART barriers and facilitators do you see in your practice? What questions do you have about LA ART implementation? Leave a comment to join the discussion!