HIV Long-Acting Injectables Face Policy Hurdles After CROI 2025
Amid the political turmoil and public health uncertainties of 2025, a remarkable scientific success story continues to unfold. The Conference on Retroviruses and Opportunistic Infections (CROI 2025) showcased significant advancements in HIV long-acting injectables for prevention and treatment—with new formulations requiring as few as one intervention per year. These latest innovations build on the promise of existing long-acting therapies while dramatically extending their duration and effectiveness.
These advancements represent more than scientific achievements; they're testaments to the HIV community's persistent demand for better options. After decades of daily pills, these innovations offer liberation from medication schedules, reduced visibility for those who face stigma, and new hope for those who struggle with adherence. The HIV community has always adapted and persevered, and these breakthroughs are the latest chapter in that ongoing story of resilience.
Yet, as we celebrate these scientific milestones, we face a familiar challenge: ensuring innovations translate into accessible care for all who need it. While researchers present promising data in conference halls, Republican-led attempts to slash Medicaid funding and legal challenges to preventive care coverage threaten to limit who benefits from these breakthroughs. It's a jarring disconnect between scientific progress and political reality that the HIV community knows all too well.
Still, if history has taught us anything, it's that the HIV community has never backed down from a fight for access. So we'll toast to the science, roll up our sleeves, and get to work on the policy—because breakthrough treatments mean little if they're out of reach for those who need them most.
Scientific Breakthroughs in HIV Prevention
The most notable announcement from CROI 2025 was Gilead's presentation of first clinical data for once-yearly lenacapavir formulations for HIV prevention. The Phase 1 study data showed that both intramuscular formulations maintained plasma concentrations well above protective thresholds for a full year, with median trough concentrations at Week 52 significantly higher than those observed with twice-yearly lenacapavir at Week 26.
This represents a substantial advance beyond current options like daily oral PrEP and bimonthly injectable cabotegravir, potentially reducing interventions to just once annually. The PURPOSE trials have already demonstrated the impressive efficacy of lenacapavir, with PURPOSE 1 showing 100% protection in women in South Africa and Uganda, and PURPOSE 2 finding a 96% lower acquisition rate compared to background incidence across diverse populations.
Advancements in Long-Acting HIV Treatment
Treatment options for people living with HIV are seeing similar progress. The combination of lenacapavir with broadly neutralizing antibodies (bNAbs) teropavimab and zinlirvimab maintained viral suppression in 96% of participants at Week 26, comparable to daily oral treatment. This regimen, which gained FDA Breakthrough Therapy Designation in January 2025, could offer a complete twice-yearly treatment option.
ViiV Healthcare's EMBRACE study of N6LS, administered every four months with monthly cabotegravir, showed similarly high rates of viral suppression. A UCSF study further confirmed the value of long-acting injectables, with 98% viral suppression after 48 weeks among patients who previously struggled with oral medication.
Diverse Patient Preferences
Research confirms that preferences for HIV treatment vary significantly. A recent study identified three distinct preference groups: those preferring implants (29%), those preferring long-acting oral or injectable options (35%), and those preferring daily or long-acting oral treatments (36%). These preferences correlated with factors like age, education, injection aversion, and adherence to current therapy.
This heterogeneity underscores that "the failure of current daily oral ART to achieve viral suppression for all people living with HIV has shown that there is no one-size-fits-all in HIV care." Offering a range of options will be essential to address diverse needs and preferences, potentially improving both adherence and outcomes.
Access Barriers and Coverage Challenges
Despite the promising scientific advances in long-acting treatment and prevention therapies, significant structural barriers threaten to limit their reach to the communities that need them most. The complex distribution and administration requirements for these medications create unique challenges not seen with oral HIV medications.
According to data from NASTAD, the Wholesale Acquisition Cost (WAC) for Apretude (cabotegravir for PrEP) is $3,700 per dosing kit, translating to approximately $22,200 annually for maintenance doses, or about $25,900 for the first year with initiation doses. This cost, while lower than the $40,000 often cited for Cabenuva (the treatment version), remains substantially higher than generic oral PrEP. Unlike oral medications, these injectable options also require additional costs for clinic visits and administration fees, further complicating access.
For people relying on AIDS Drug Assistance Programs (ADAPs), coverage remains inconsistent. According to the International Association of Providers of AIDS Care (IAPAC), six states (Missouri, Kentucky, Louisiana, Oklahoma, Texas, and South Dakota) and some U.S. territories do not cover injectable HIV medications through their ADAP programs. Even in states that do provide coverage, the distribution system for these medications differs significantly from oral medications. As NASTAD explains, long-acting injectables are distributed through "buy-and-bill," "white bagging," or "clear bagging" mechanisms involving specialty distributors or pharmacies rather than traditional retail pharmacies, creating additional logistical barriers.
While the Biden Administration issued updated guidance in October 2024 requiring health insurers to cover all three FDA-approved forms of PrEP without cost-sharing, this mandate faces legal challenges. The Supreme Court has agreed to hear a lawsuit challenging the Affordable Care Act's preventive services provision, with arguments commencing in spring 2025 and a decision expected by July. This case could potentially eliminate the requirement for insurance plans to cover preventive services like PrEP without cost-sharing.
These access challenges disproportionately affect those at highest risk for HIV. Despite the recommendations for PrEP that now include newer formulations, PrEP uptake remains unequal. The Centers for Disease Control and Prevention (CDC) has estimated that the proportion of persons with indications for PrEP who received it was 60.5% among White persons vs 7.9% in Black persons and 13.8% in Hispanic/Latino persons. Without policy intervention to address these barriers, the remarkable scientific progress in HIV prevention and treatment risks benefiting only those with privileged access to healthcare while leaving behind the communities with the greatest need.
Political Context and Threats to Progress
The current political landscape presents additional challenges to expanding access to long-acting injectables for HIV treatment and prevention. The Republican-led Congress is considering plans to cut Medicaid by potentially $880 billion or more to help pay for tax cuts, according to a Kaiser Family Foundation report. Such reductions would likely impact access to these innovative but costly treatments.
At the international level, the Trump administration's pause on PEPFAR-funded prevention services threatens to reverse progress in global HIV prevention efforts. As Jirair Ratevosian writes in his CROI analysis, "The Trump administration now faces a choice: either let PEPFAR's legacy crumble or seize this opportunity to lead the next phase of HIV prevention."
It's worth noting that Medicaid enrollees across the political spectrum express concerns about potential program cuts. KFF focus groups found that "both Trump and Harris voters valued their Medicaid coverage and the access to health care services, mental health services, and medications for themselves and their children it provides." Participants described losing Medicaid as potentially "devastating" and likely to lead to serious consequences for their physical and mental health.
Bridging the Gap
To ensure equitable access to these breakthrough HIV prevention and treatment options, several policy approaches should be considered:
Strengthen CMS Guidance on Long-Acting Injectables: The Centers for Medicare & Medicaid Services should update its informational bulletins on HIV prevention and care delivery to reflect the latest advancements in longer-acting therapies and issue specific policy guidance on Medicaid's role in supporting PrEP uptake and persistence.
Defend Preventive Service Coverage: Advocacy efforts should focus on defending the ACA's preventive services mandate as the Supreme Court considers challenges to this provision.
Expand ADAP Coverage: State ADAP programs that do not currently cover long-acting injectables should be encouraged to add these medications to their formularies, potentially with additional federal support to offset costs.
Engage in Value Assessment: Payers, including Medicaid and Medicare, should evaluate the long-term clinical and economic benefits of these options, including reduced transmission, improved quality of life, and potentially fewer hospitalizations due to better adherence.
Conclusion
The scientific advancements presented at CROI 2025 offer unprecedented opportunities to transform HIV prevention and treatment. Once-yearly prevention therapies and twice-yearly treatment regimens could dramatically improve adherence, reduce transmission, and enhance quality of life for millions of people living with or at risk for HIV.
However, without concerted policy action to address access barriers, these innovations risk becoming available only to those with privileged access to healthcare, potentially widening rather than narrowing health disparities. As long-acting HIV therapies move closer to widespread availability, advocates, policymakers, healthcare providers, and industry partners must work together to ensure that these scientific breakthroughs translate into public health impact for all communities affected by HIV.
The gap between what's scientifically possible and what's accessible represents both a policy failure and a moral challenge. Bridging this gap requires political will, innovative financing approaches, and a commitment to health equity that matches the remarkable scientific progress we've witnessed.
Breakthroughs in HIV Research from CROI 2024
This month, the global health community convened at the Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, spotlighting groundbreaking advancements in HIV research and treatment. This year's conference highlighted significant progress in long-acting HIV therapies and innovative strategies for pediatric HIV care, pointing towards a future where HIV management is more effective and less burdensome.
Key discussions focused on the success of long-acting treatments like Cabenuva (cabotegravir and rilpivirine), which have demonstrated remarkable efficacy in clinical trials, offering new hope for those challenged by daily medication regimens. These developments promise to enhance adherence and improve the quality of life for millions living with HIV.
Advancements in HIV prevention were also notable, with the introduction of once-weekly oral treatments and the confirmation of safety for HIV prevention methods during pregnancy. These innovations expand the tools available to combat HIV transmission and emphasize the need for accessible and inclusive prevention strategies.
Additionally, the conference highlighted the importance of addressing co-occurring conditions such as liver disease and cardiovascular risks in people living with HIV. The exploration of pediatric HIV treatment also showed promising paths towards ART-free remission in children, potentially leading to a cure for young patients.
The role of community-engaged research was underscored, ensuring that the developments reflect the needs and voices of those most affected by HIV. The insights from CROI 2024 mark a path forward in the HIV fight, characterized by innovation, collaboration, and a commitment to enhancing the lives of those impacted by the virus.
Advancements in Long-Acting HIV Treatments
The landscape of HIV treatment and prevention is undergoing a significant transformation, heralded by the advent of long-acting therapies. These innovations promise a new era of convenience and efficacy, potentially changing the lives of millions of people living with HIV (PLWH) worldwide.
At the forefront of this shift are long-acting injectable treatments, such as Cabenuva (cabotegravir and rilpivirine), which have demonstrated remarkable success in clinical trials. A new study reveals that "These findings open up new possibilities for millions of people with HIV, particularly those whose health suffers due to challenges of daily pill taking." This statement underscores the potential of long-acting injectables to revolutionize HIV treatment by alleviating the daily burden of pill-taking, with more than 90% of participants receiving their injections on time.
The development of ultra-long-acting formulations, such as the cabotegravir injection for HIV prevention, represents another leap forward. With a predicted half-life significantly longer than existing formulations, these treatments offer the promise of even greater adherence and convenience, potentially reducing the frequency of dosing to just 3 times a year.
Moreover, the integration of broadly neutralizing antibodies (bnAbs) with long-acting antiretrovirals is opening new avenues for more durable treatment options. As Liz Highleyman summarizes, "Broadly neutralizing antibodies appear to work well with lenacapavir or cabotegravir in long-acting regimens for HIV treatment, but studies are still in early stages." This collaboration between bnAbs and long-acting antiretrovirals has shown promising results, with studies reporting up to 95% of participants maintaining viral suppression.
Apart from injectable treatment options, the introduction of a once-weekly oral HIV treatment presents another long-acting option for patients who prefer treatment without needles. The convenience of a once-weekly regimen cannot be overstated, with one researcher emphasizing the importance of such developments: "Developing once-weekly treatment options could help meet the needs of each person, aiming toward maximizing long-term outcomes for people with HIV." This approach has demonstrated remarkable efficacy, with over 90% of participants maintaining viral suppression, showcasing the potential of once-weekly treatments to significantly enhance adherence and, consequently, the effectiveness of HIV treatment.
Breakthroughs in HIV Prevention
In addition to advancements in treatment regimens, significant progress has been made in ensuring the safety of HIV prevention methods during pregnancy. The use of the vaginal ring and oral PrEP has been thoroughly evaluated, with findings affirming their safety for pregnant women—a critical consideration given the increased vulnerability to HIV infection during pregnancy. Remarkably, "95% of deliveries were at term and 4% were preterm, with no study participants acquiring HIV," highlighting the effectiveness and safety of these prevention tools in protecting both mothers and their unborn children from HIV.
Furthermore, the Together Take Me Home project has made significant strides in expanding access to HIV prevention through the distribution of HIV self-test kits. In just nine months, the project saw over 181,558 orders placed, with 337,812 tests distributed, many to people who had never tested for HIV or had not tested in over a year. Sixty percent of all orders contained enough information to describe participants, with 61% from men reporting male partners in the past 12 months, 10.7% from gender-diverse persons, and 10% from Black women. This initiative underscores the importance of meeting people where they are, providing accessible and confidential testing options. As Dr. Neblett Fanfair noted, "This shows how impactful this is to meet people where they are with what they need to be met with. We’re really excited that it’s not just about HIV self-tests, but it also opens the door to STI testing and PrEP as well," highlighting the project's role in broadening the reach of HIV prevention efforts.
Addressing Co-Occurring Conditions
The intersection of HIV with other health conditions underscores the complexity of care required for people living with HIV. Recent research has brought to light significant advancements in addressing co-occurring conditions, such as liver disease and cardiovascular risks.
A groundbreaking study on the use of semaglutide has shown promising results in reducing the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV. MASLD, characterized by excessive fat accumulation in the liver, poses a significant risk of progressing to more severe liver diseases. The introduction of semaglutide, a medication initially used for diabetes and weight management, into the treatment regimen for PLWH has marked a notable advancement, with participants experiencing "an average 31% reduction in liver fat." This significant decrease highlights semaglutide's potential as a therapeutic agent in managing liver health in people living with HIV.
Furthermore, the issue of cardiovascular health in PLWH has been brought to the forefront by recent findings indicating that current tools may significantly underestimate the risk of cardiovascular events in this population. Notably, "Cardiovascular event rates were higher overall, with cisgender women experiencing about two and a half times more events than predicted." This discrepancy underscores the need for more accurate assessment tools and tailored prevention strategies to mitigate the elevated risk of cardiovascular diseases among people living with HIV.
Additionally, research into prostate cancer screening among men with HIV has revealed a concerning "screening gap." According to a study, men with HIV were significantly less likely to receive PSA screening prior to diagnosis, leading to a higher incidence of advanced prostate cancer at the time of diagnosis. This gap in screening and early detection highlights the need for increased awareness and proactive screening measures for men living with HIV, to ensure timely diagnosis and treatment of prostate cancer.
Innovations in Pediatric HIV Treatment
Pediatric HIV treatment is witnessing remarkable innovations, particularly in the areas of early treatment and the exploration of long-acting therapies. These advancements are not only enhancing the quality of life for children living with HIV but also paving the way toward potential remission and a future where daily medication may not be necessary.
In a new study highlighted in POZ and further discussed on HIV.gov has brought to light the significant potential of initiating ART within the first days of life. This approach has led to ART-free remission in some cases, with "four of the six children achieving ART-free remission." Such findings are groundbreaking, as they suggest that early intervention can drastically alter the course of HIV in children, offering a glimpse into the possibility of a cure or long-term remission. The impact of these results cannot be overstated, as they represent a monumental step forward in the quest to end HIV as a lifelong condition.
Further extending the scope of pediatric HIV treatment, recent research has also explored the benefits of long-acting HIV treatments for adolescents. Long-acting, injectable antiretroviral therapy has been found safe and effective in adolescents with HIV viral suppression. This study marks the first instance where adolescents with HIV have an alternative to daily pills for treatment, showcasing very encouraging outcomes. All participants in the study remained virally suppressed, and none experienced serious adverse events related to the drug regimen. This advancement is particularly significant as it addresses one of the major challenges in adolescent HIV care—adherence to daily medication. By providing a less frequent dosing schedule, long-acting treatments can significantly ease the treatment burden on young patients and their families.
Community-Engaged Research and Future Directions
These groundbreaking advancements in HIV research and treatment are increasingly being achieved thanks to community-engaged research. This approach not only enriches the research process but ensures that the outcomes are more aligned with the needs and realities of those most affected by HIV. Dr. LaRon Nelson's insights underscore the critical role of community involvement: "If we don’t have community voices or engaged communities, we aren’t going to be asking the right questions." This perspective highlights the indispensable value of incorporating diverse community experiences and insights into the research process, ensuring that the studies conducted are both relevant and impactful.
A prime example of the success of community-engaged research is the implementation and study of Doxy-PEP (doxycycline post-exposure prophylaxis) for the prevention of sexually transmitted infections (STIs) alongside HIV. Research and real-world application in San Francisco have demonstrated remarkable outcomes, with bacterial STIs decreasing by nearly 60% in less than a year at the San Francisco AIDS Foundation’s (SFAF) clinic. This significant reduction showcases the potential of community-engaged approaches in addressing public health challenges effectively. The collaboration between researchers, healthcare providers, and community members facilitated the rollout of Doxy-PEP, leading to substantial public health benefits.
Furthermore, the ongoing exploration of HIV vaccine research represents another frontier where community engagement is vital. As discussed in HIV.gov’s updates from CROI 2024, the development and testing of HIV vaccines are critical to the future of HIV prevention. Engaging communities in this research not only helps in designing more effective studies but also in building trust and ensuring broader acceptance and uptake of future vaccines.
Conclusion
CROI 2024 showcased significant progress in HIV research, highlighting innovations in long-acting treatments, prevention strategies, and care for co-occurring conditions and pediatric HIV. These advancements signal a shift towards more effective, less burdensome HIV management, tailored to meet diverse needs. They not only aim to improve the lives of millions living with HIV but also to significantly reduce new infections.
These developments are the culmination of years of research, collaboration, and community engagement, emphasizing the crucial role of community-involved research in addressing the real needs and voices of those affected by HIV.
To fully leverage these breakthroughs, continued research investment and stronger community partnerships are vital. We're at the cusp of a new era in HIV care, characterized by innovative treatments and comprehensive prevention efforts, all geared towards improving the lives of those living with or at risk for HIV. While these innovations are welcomed, necessary, and exciting, we must also recognize the policy landscape that affects access to care. In order to End the Epidemic, we must ensure consistent, open, equal access to individualized care and medications.