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.
DoxyPEP's Impact: New Evidence Shows Promise and Challenges in STI Prevention
After nearly two decades of rising sexually transmitted infection (STI) rates in the United States, the Centers for Disease Control & Prevention (CDC) 2023 surveillance report reveals a welcome shift: overall STI rates dropped by 1.8% from 2022 to 2023. Gonorrhea cases declined by 7% for the second straight year, and primary and secondary syphilis fell by 10%—marking the first significant decrease in more than two decades. While these figures offer cautious optimism, questions remain about how best to sustain momentum, especially amid ongoing concerns about antimicrobial resistance and unequal access to prevention resources.
One potentially transformative intervention gaining traction is doxycycline post-exposure prophylaxis (doxyPEP). The CDC’s 2024 guidelines recommend doxyPEP for gay, bisexual, and other men who have sex with men (MSM), as well as transgender women, who have experienced a bacterial STI in the past year. Although clinical trials showed promising efficacy against chlamydia and syphilis, real-world data underscore nuanced challenges related to resistance, health disparities, and local healthcare capacity.
The Changing Landscape of STI Prevention
Several initiatives set the stage for the recent slowdown in STI rates. The American Rescue Plan Act of 2021 provided funding to strengthen the disease intervention specialist workforce, bolstering capacity for targeted contact tracing and clinical follow-up. These efforts were amplified by new CDC recommendations that formalized doxyPEP for specific high-risk groups.
San Francisco became an early adopter of doxyPEP guidelines in October 2022, leveraging its established HIV prevention infrastructure and community partnerships. Early clinical trial data had shown marked drops in chlamydia and syphilis, prompting local officials to adopt prophylactic antibiotic use despite concerns over potential misuse and growing gonococcal resistance. Their experience would soon be mirrored and examined in other healthcare settings.
Real-World Evidence: San Francisco and Kaiser Permanente
Two new studies illuminate the impact of doxyPEP beyond controlled clinical environments. The first, conducted by the San Francisco Department of Public Health, examined STI rates before and after the city’s 2022 adoption of doxyPEP guidelines. Investigators reported a 49.6% drop in chlamydia and a 51.4% decline in early syphilis compared to what forecasts had predicted. Three sentinel STI clinics observed that 19.5% of eligible gay, bisexual, and other men who have sex with men, as well as transgender women, initiated doxyPEP—a relatively high uptake for a new intervention.
A complementary Kaiser Permanente Northern California study included more than 11,000 participants already on HIV pre-exposure prophylaxis (PrEP). Those who added doxyPEP to their prevention repertoire saw chlamydia rates fall from 9.6% to 2.0% every quarter, while syphilis rates declined from 1.7% to 0.3%. These improvements closely mirrored prior clinical trial data, underscoring doxyPEP’s real-world effectiveness in high-risk populations.
However, the two studies diverged in their findings on gonorrhea. San Francisco observed a 25.6% increase in gonorrhea cases among the doxyPEP group, while Kaiser Permanente achieved a modest 12% reduction. Even in the latter setting, the intervention had varying efficacy based on infection site, with minimal impact on pharyngeal gonorrhea. Researchers attribute these discrepancies to existing tetracycline resistance patterns, which can range from 20% in U.S. gonorrhea strains to over 50% in certain regions globally.
Key Challenges to Implementation
1. Antimicrobial Resistance
Chief among concerns is the capacity of gonorrhea and other pathogens to develop resistance to tetracyclines. A modeling study in The Lancet warns that if doxyPEP achieves very high uptake—around 90%—it could lose effectiveness within just 1.6 years. More moderate adoption might prolong utility but still faces the ever-present risk that gonococcal strains could quickly evolve. The tension between scaling up prophylaxis to curb infections and preserving antibiotic utility for the long term remains a core dilemma for public health agencies.
2. Limited Healthcare Infrastructure
Successfully rolling out doxyPEP also requires robust clinical infrastructures. San Francisco’s early adoption relied on specialized STI clinics, disease intervention specialists, and strong community engagement. Such resources are scarce in many rural areas and underresourced urban centers, where STI burdens are often high. Without targeted funding and workforce development, these regions may fail to realize the potential benefits of prophylaxis. This gap underscores why a one-size-fits-all strategy for doxyPEP is unlikely to work uniformly nationwide.
3. Cost and Insurance Access
The Kaiser Permanente experience highlighted how commercial insurance coverage can determine doxyPEP uptake. Though Kaiser found no racial or ethnic disparities in its cohort, the ability to pay for routine tests and antibiotics remains a significant hurdle for many. Nearly half of all new STIs affect patients aged 15–24, a demographic often lacking stable insurance. Safety-net providers, such as community clinics and public health agencies, will need additional resources to prevent cost barriers from fueling inequities in STI prevention.
Addressing Health Equity
Disparities in STI burden persist despite national declines. CDC data show that Black communities—though comprising just 12.6% of the population—face roughly a third of all reported STIs, and American Indian and Alaska Native populations have the highest rates of syphilis. These patterns reflect structural inequities, from healthcare access to economic stability. DoxyPEP, if expanded, could either narrow or widen these gaps, depending on implementation strategies.
For example, the San Francisco Department of Public Health’s success relied on partnerships with community-based organizations that serve LGBTQ+ populations, bilingual outreach, and peer educators who could directly address stigma. Similar culturally tailored approaches will be crucial elsewhere. Nationally, any prophylaxis effort must acknowledge social determinants of health, from limited insurance coverage to historical medical mistrust, as central issues in achieving equitable outcomes.
Policy Recommendations
Meeting these challenges head-on requires collaboration among federal agencies, healthcare systems, and local organizations. Four policy domains stand out:
Robust Surveillance and Resistance Tracking
Establish or enhance regional testing to promptly detect shifts in gonococcal resistance.
Standardize reporting on doxyPEP uptake, stratifying data by race, ethnicity, and insurance status to monitor equity.
Integrated Healthcare Delivery
Incorporate doxyPEP into existing HIV PrEP programs, leveraging shared clinical workflows for ongoing STI screening.
Provide decision-support tools to guide providers in identifying those most likely to benefit from prophylaxis and in understanding local resistance rates.
Financing and Insurance Coverage
Secure coverage mandates or subsidies so that the costs of antibiotics and regular STI tests do not fall disproportionately on those most at risk.
Offer grants or incentives for safety-net clinics to scale up prevention services, including patient education and follow-up testing.
Antimicrobial Stewardship and Patient Education
Develop guidelines for targeted doxyPEP use to minimize unnecessary exposure—especially for gonorrhea, given its evolving resistance.
Emphasize correct usage and follow-up testing in patient education to ensure prophylaxis remains effective and that potential side effects are promptly reported.
Looking Ahead: Balancing Innovation and Stewardship
DoxyPEP’s success in specific cohorts highlights how targeted prophylaxis can substantially reduce chlamydia and syphilis infections. However, higher gonococcal resistance in some locales points to the need for continual surveillance and swift policy adjustments. Achieving a balance between curbing acute STI outbreaks and safeguarding long-term antibiotic effectiveness will require:
Adaptive Guidelines: Quickly revising prescribing recommendations if local data reveal resistance spikes.
Equitable Implementation: Ensuring consistent uptake in historically underserved communities, rather than concentrating benefits among those with robust insurance.
Global Collaboration: Sharing best practices and emerging data to keep pace with evolving gonococcal strains and develop new therapeutic agents or vaccines.
Conclusion
The modest national declines in STI rates are a reminder that with strategic investments and coordinated interventions, progress is possible. DoxyPEP stands out as a promising addition to the prevention toolbox—particularly for chlamydia and syphilis—when backed by sufficient testing, monitoring, and community outreach. Yet the specter of antimicrobial resistance, along with ongoing disparities in healthcare access, underscores that a single biomedical solution must be carefully managed.
Findings from San Francisco and Kaiser Permanente prove doxyPEP can effectively reduce STI incidence in real-world settings. Whether it remains a durable tool will depend on collective commitment: policymakers must fund surveillance and outreach, clinicians must practice stewardship, and communities must engage to ensure equitable access. If implemented wisely, doxyPEP could shape a future where the burden of STIs—and the inequalities that fuel them—diminish, showcasing how targeted prevention strategies can enhance public health without jeopardizing our arsenal of antibiotics.