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.
