Equitable Access to Long-Acting HIV Treatment
For people living with HIV (PLWH), adherence to antiretroviral therapy (ART) is crucial. Achieving and maintaining viral suppression, the primary goal of HIV treatment, depends on taking medication as prescribed. Yet, consistent adherence can be challenging due to busy schedules, pill fatigue, stigma, and side effects. Suboptimal adherence has serious consequences, including increased viral load rebound, drug resistance, and disease progression. It also hinders public health efforts to control the HIV epidemic. Long-acting injectable (LAIs) antiretroviral therapies offer a promising alternative by providing sustained viral suppression with less frequent dosing. However, a significant barrier remains: equitable access. Some State AIDS Drug Assistance Programs (ADAPs), designed to support low-income PLWH, do not adequately cover these medications due to cost concerns .
This limited coverage is a public health issue and a moral failing. State ADAPs must provide equitable access to the most effective HIV treatments available that meet the unique needs of the patient, regardless of cost. While the initial expense of LAIs may be high, their potential to improve adherence, viral suppression, and long-term health outcomes far outweighs the financial investment. It's time for ADAPs to prioritize the health of PLWH by ensuring access to LAIs and supporting efforts to end the HIV epidemic.
The Promise of LAIs
LAIs represent a major advancement in HIV treatment. Unlike daily oral ART, which requires daily ingestion and absorption, LAIs are administered as intramuscular injections, typically once a month or every two months. These injections provide a steady release of medication, ensuring consistent drug levels and effective viral suppression.
The benefits of LAIs are significant. The MOCHA study found that adolescents overwhelmingly favored LAIs due to the convenience of less frequent dosing . This reduces the daily burden of remembering to take pills, leading to improved adherence rates—a key factor for successful HIV treatment.
Improved adherence through LAIs also enhances long-term health outcomes and reduces the risk of HIV transmission. When the virus is undetectable, it cannot be sexually transmitted, a concept known as Undetectable = Untransmittable (U=U). By promoting optimal adherence and sustained viral suppression, LAIs become a powerful tool in the fight against the HIV epidemic.
Evidence of Effectiveness
The effectiveness of LAIs is supported by considerable scientific evidence. The MOCHA study found that after 24 weeks of treatment with long-acting cabotegravir/rilpivirine, none of the nearly 150 participants experienced virological failure. This highlights the potential of LAIs to achieve durable viral suppression, especially among younger populations who often struggle with adherence to daily oral regimens.
The LATITUDE study, focusing on PLWH with a history of suboptimal adherence to oral ART, found that long-acting injectable therapy was superior in suppressing HIV replication compared to daily oral medication . The compelling results led the National Institutes of Health Data and Safety Monitoring Board to recommend offering the long-acting medication to all eligible participants.
These studies, along with a growing body of research, show that LAIs are effective in achieving viral suppression and are particularly beneficial for those who struggle with adherence to traditional oral ART. This makes LAIs a critical tool for addressing disparities in HIV treatment outcomes and advancing health equity among PLWH.
Impact on the HIV Epidemic
The effectiveness of LAIs in maintaining viral suppression has significant implications for public health, especially the Ending the HIV Epidemic (EHE) initiative, which aims to reduce new HIV infections in the United States by 90% by 2030. Achieving this goal requires expanding access to effective prevention and treatment options.
LAIs support this effort by fostering optimal adherence and sustained viral suppression. By ensuring that PLWH have access to medications that effectively suppress the virus, we improve health outcomes and reduce the likelihood of transmission, moving closer to the EHE goal.
LAIs also align with the 95-95-95 targets set by UNAIDS, adopted by the EHE initiative, which aim to ensure that 95% of PLWH know their status, 95% of those diagnosed receive sustained ART, and 95% of those on treatment achieve viral suppression. By improving adherence and facilitating viral suppression, LAIs contribute to achieving these targets and reducing new cases.
The International Association of Providers of AIDS Care (IAPAC) emphasized the importance of LAI access for supporting the goals of the Fast-Track Cities initiative . This initiative aims to accelerate progress towards ending the HIV epidemic at the local level. IAPAC argues that providing PLWH with access to effective ART options like LAIs is essential for achieving these ambitious targets.
The Cost Conundrum
The benefits of LAIs are often overshadowed by concerns about cost. Critics, including some state ADAP administrators, point to the high upfront price of these medications compared to generic oral ART options. A 2023 article on AIDSmap highlighted that the price of long-acting cabotegravir would need to drop considerably to be cost-effective compared to daily oral PrEP . This concern about cost is echoed in discussions surrounding LAIs for treatment, with some stakeholders questioning whether the potential benefits justify the higher price tag.
A recent article in TheBody revealed that the annual cost of Cabenuva, a commonly prescribed LAI, is approximately $40,000. This figure highlights the need for careful consideration of drug pricing within ADAP formularies. For comparison, the annual retail cost of the popular oral ART treatment Biktarvy is just over $50,000. However, as of January 2023, only 78% of state ADAPs covered Cabenuva.
This gap in coverage disproportionately affects the most vulnerable PLWH. In states without Cabenuva coverage, nearly two-thirds of ADAP clients live at or below the federal poverty level, compared to 43% in states with coverage. Additionally, ADAP clients in states lacking Cabenuva coverage are more likely to be Black or Hispanic .
While cost is a valid concern, focusing solely on upfront expenses overlooks the potential for long-term savings. ADAPs can negotiate lower drug prices and must consider the broader economic and public health benefits of LAIs.
A Holistic Cost-Benefit Analysis
A comprehensive cost-benefit analysis must consider the long-term impact on healthcare expenditures and public health outcomes. A narrow focus on upfront costs ignores the potential of LAIs to generate significant savings over time.
The HIV+Hepatitis Policy Institute modeled the impact of long-acting PrEP on HIV case aversion and medical cost savings, concluding that improved adherence leads to better health outcomes and reduced transmission, ultimately saving costs for the healthcare system. They projected that increased uptake of long-acting PrEP would avert 139,296 person-years of HIV treatment over ten years, saving $4.25 billion .
Preventing new HIV infections through improved adherence not only saves on direct treatment costs but also reduces the need for costly interventions related to managing complications and comorbidities of advanced HIV. By minimizing the risk of transmission, LAIs contribute to a decrease in HIV prevalence, further reducing long-term healthcare costs and saving lives in the process.
Intangible Benefits
The benefits of LAIs extend beyond economics. These medications significantly improve the quality of life and overall well-being of PLWH.
The MOCHA study highlighted that young people preferred LAIs due to reduced treatment anxiety and fatigue. They appreciated the increased privacy, as they no longer needed to take daily pills that might disclose their HIV status.
ADAP Advocacy emphasizes the importance of patient empowerment and choice in HIV care. LAIs provide PLWH with greater autonomy in managing their health, aligning treatment with their personal needs and lifestyles. This sense of control improves mental health, self-esteem, and quality of life.
By reducing the frequency of medication-related tasks, LAIs help minimize the stigma associated with HIV. Daily pill-taking can serve as a constant reminder of one's HIV status, triggering feelings of shame or fear of disclosure. LAIs, with less frequent dosing, allow PLWH to integrate their care more seamlessly into their lives, reducing the psychological burden.
These intangible benefits, while difficult to quantify economically, should weighed equally when making decisions that affect patient care and access. They highlight the profound impact of LAIs on the lives of PLWH, extending beyond viral suppression to encompass improved quality of life, reduced stigma, and increased autonomy.
Ethical Considerations
Equitable access to LAIs is an ethical imperative. State ADAPs, as safety-net programs for low-income PLWH, have a moral duty to provide access to the most effective HIV treatments, regardless of cost. Denying access based on price perpetuates health disparities and undermines equity.
IAPAC argues that access to innovative treatments like LAI-ART should not depend on socioeconomic status. Providing ADAP coverage for LAIs is crucial for equitable healthcare.
Restricting LAI access disproportionately impacts those already facing systemic barriers, including people of color, those with low income, and those in rural areas. These populations are more likely to have adherence challenges due to social, economic, and structural factors. Denying them access to LAIs further entrenches health inequities.
A commitment to health equity demands prioritizing the needs of the most vulnerable. Cost concerns, while valid, cannot justify denying essential healthcare to those who need it most. State ADAPs must ensure all PLWH can benefit from LAIs, regardless of financial circumstances.
Addressing Barriers and Implementing Solutions
Ensuring equitable access to LAIs requires a multi-faceted approach, addressing cost concerns and systemic barriers. Policy changes at federal and state levels are necessary for creating a more just healthcare system for PLWH.
Policy Recommendations for ADAPs
Mandate LAI Coverage: State legislatures should require ADAPs to cover all FDA-approved LAIs for HIV treatment. This would ensure all eligible PLWH have access to these medications.
Streamline Prior Authorization: ADAPs should streamline prior authorization processes for LAIs, minimizing delays and ensuring timely access to treatment. This could include standardized approval criteria, expedited review processes, and clear communication between providers and ADAP administrators.
Increase Funding Allocations: State and federal governments must prioritize increased funding for ADAPs, recognizing the growing demand for LAIs and their long-term cost savings potential.
Provider Education and Training
The ADAP Advocacy Association underscores the need for robust provider education and training on LAIs. They advocate for targeted education about providing LAIs within a modified clinic flow model.
Ongoing education initiatives should focus on:
LAI Pharmacology and Administration: Providers need a thorough understanding of LAIs, including dosing schedules, potential side effects, and proper administration techniques.
Patient Selection and Counseling: Training should equip providers to identify appropriate candidates for LAIs, considering personalized patient needs and potential adherence barriers. Effective counseling strategies are necessary for addressing concerns and ensuring informed decisions.
Addressing Provider Bias: Some providers may hold misconceptions about LAIs, such as concerns about patient acceptance or injection-related anxiety. Training programs should address these biases, providing evidence-based information and dispelling myths.
By investing in comprehensive provider education and training, we can empower healthcare professionals to embrace LAIs confidently, facilitating broader access and improved health outcomes for PLWH.
Patient Advocacy and Support
Community activism has been a hallmark of the U.S. HIV response, and PLWH should work with clinicians to advocate for state ADAPs to prioritize patient choice and treatment preferences.
PLWH and community organizations can play a powerful role by:
Sharing Their Stories: Personal narratives are powerful tools for raising awareness and influencing policy change. PLWH who have benefited from LAIs can highlight the positive impact, while those denied access can shed light on the challenges and the need for equitable coverage.
Engaging with ADAP Advisory Committees: Many state ADAPs have advisory committees of stakeholders, including PLWH. Participating in these committees provides an opportunity to voice concerns and advocate for policy changes.
Collaborating with Advocacy Organizations: Partnering with national and local organizations can amplify voices, provide resources, and facilitate collective action for policy changes.
Educating Their Peers: PLWH can educate peers about LAIs, dispelling myths and sharing information about the benefits and potential challenges. Peer-to-peer support can empower people to advocate for their health and make informed treatment decisions.
By raising voices, sharing experiences, and engaging in collective action, we can drive progress towards equitable LAI access, ensuring all can benefit from these transformative medications.
Conclusion
Long-acting injectable antiretroviral therapies (LAIs) represent a major advancement in HIV treatment, offering a powerful tool for improving adherence, achieving sustained viral suppression, and ending the HIV epidemic. While cost concerns are valid, a holistic cost-benefit analysis shows that the long-term benefits of LAIs far outweigh the initial investment.
The time for action is now. Contact your state legislators, ADAP representatives, and other stakeholders. Demand equitable LAI coverage and support policies that prioritize the health and well-being of all PLWH. Together, we can dismantle barriers to access and ensure no one is left behind in the fight to end the HIV epidemic.
European Commission Approves Once Every 6 Month Supplemental HIV-Treatment
Last week, the European Commission (EC) approved use of Gilead Sciences’ investigational medication, lenacapavir (branded as Sunlenca), for use in treatment for people whose HIV is highly treatment resistant. Lenacapvir has been closely watched by advocates because of great anticipation regarding injectable and otherwise long-acting agents (LAAs) and because of its exceptionally long half-life in the body, providing efficacy for about 6 months from just one subcutaneous injection, providing a potential for the longest acting agent to hit the market thus far.
Lenacapavir also stands out as a first-in-class product because it works in a way that no other antiretroviral medication works. Offering a novel mechanism of action, binding the shell (capsid) surrounding viral genetic material that highjacks our own cells in HIV reproduction, capsid inhibitors will work against HIV in multiple areas of the virus’ life cycle. And because this is a tool we’ve never used before, it’s ideal for meeting the treatment needs of people living with highly resistance HIV – the virus doesn’t recognize the medication and has not yet found a way around it. Because HIV is highly adaptable, that lack of resistance may be short-lived once broad reach of the product is made available but excitement remains for a novel product, especially for people who have developed such resistance that options of effective care have diminished to near zero.
Gilead Sciences is awaiting a decision from the United States’ Food and Drug Administration (FDA) on its recently resubmitted “New Drug Application” (NDA), after the agency declined to accept the NDA due to issues with the glass vials used for the injectable form of the medication. The vial issue has since been fixed and research resumed for use of lenacapavir as a supplement to “background” treatment, first-line treatment, and as pre-exposure prophylaxis (PrEP). At the end of July, the FDA provided Gilead with a December 27, 2022 prescription drug user fee date. This is one of the final steps in an initial new drug approval. (Briefly, the Prescription Drug User Fee Act funds a massive portion of the FDA and those medications which pose potential benefit to public health may receive an expedited fee date; HIV advocates historically championed the act as a massive “win” in the early 90’s when introducing this funding scheme sped up their processes to make oncology and HIV medications more readily accessible.)
Patients who may hear about “once every 6-month treatment) should be kindly reminded lenacapavir will serve only as a supplement to other therapies – administering the medication is required to be done by a provider and patients will still need to remain adherent to their existing treatment regimen. HIV medications for treatment need between 2 and 3 different combinations of medications and PrEP only needs 1. As such, there may be a disparity in lenacapavir as PrEP and Sunlenca as treatment in terms of uptake because, while lenacapavir won’t require maintenance of other medications, Sunlenca as treatment will require patients to continue to take the oral medications that are “optimized” with Sunlenca acting almost like a “soft reset” for patients.
Operationalizing will remain an issue, especially for state ADAP Program’s that have not fully implemented access to cabotegravir, in terms of injectable medication management and for arguments that frame investing in successful patient care as something that requires a “cost consideration”. Patient advocates should be well-prepared to defend a desire to see this product come to their patients as those patients so desire it.
Cabenuva Approved for 2 Month Injections; Insurers Remain a Barrier to Access
In late January of 2021, ViiV Healthcare and Janssen Pharmseutical Companies announced the Food and Drug Administration’s (FDA) approval of the first extended-release injectable medication regimen for the treatment of HIV as a once-monthly administration, branded as Cabenuva. Eleven (11) months later, the FDA approved cabotegravir as an extended-release injectable suspension for the prevention of HIV as a once-every-two-month administration, branded as Apretude. Again, on February 1, 2022, the FDA expanded Cabenuva’s administration to be a once-every-two-month administration. Near overnight, people living with HIV-related medication therapy and prevention efforts went from a burdensome three-hundred sixty-five (365) pills to six (6) injections.
This kind of innovation has been long anticipated and while advocates and patients recognize not every patient will desire to switch to injectable medications and resistance profiles may require some people living with HIV to maintain their tablet regimens, injectables offer yet another tool in the tool box. The extended-release nature of injectables offer an opportunity to overcome “treatment fatigue”, reduce opportunities for missed doses and subsequent treatment resistance, and even address safety in storing medications at-home – especially for those people living with and at risk for acquiring HIV that may also be experiencing houselessness. This becomes even more of an astounding tool, in addressing disruptions in care when patients live in areas prone to natural disasters, as seen in Florida during Hurricane Michael when the state’s central pharmacy operations came to a halt, forcing the state to rely on a private-public partnership with CVS, and in Puerto Rico after Hurricane Maria, in which patients lost access to life-saving medications. The issue of natural disasters interrupting care is not new and will likely be something providers and patients need to have plans for as every indication exists climate change will produce more and more powerful hurricanes. Indeed, despite the lessons learned from Hurricane Katrina, I personally witnessed multiple calls across social media channels among people living with HIV seeking additional medication in order to manage loss of their anti-retrovirals in 2021, during Hurricane Ida. Despite the state of Louisiana and the department of Health and Human Services declaring a public health emergency and activating the Emergency Prescription Assistance Program for uninsured and underinsured patients, anecdotal reports found the program hard to manage for those who needed daily administration of medications.
Yet and still, despite these incredible advancements at our finger tips, both public and private insurance programs remain reticent to allow patient and provider choice to guide what therapies patients actually have access to. Indeed, one of the largest payers in both the public and private spaces is CVS Health, who, on December 16, 2021, published priorities in “weighing cost” versus clinical benefit while specifically naming cabotegravir as an active agent in Cabenuva and Apretude. The payer outlines tactics known as “utilization management” to include initially blocking coverage of new drugs, “strongly favor[ing] generic use”, and “select[ing a] preferred agent generating lowest net cost option in category”. Even some AIDS Drug Assistance Programs (ADAPs) are delaying adding the innovative therapy to their coverage formularies. All of which creates a system of care where people living with HIV are experiencing limitations on their access to effective therapies based on their income, rather than their need as determined by them, as patients, and their provider. Deny-first utilization management practices risk losing people to care by creating unnecessary and burdensome administrative process and delays.
When Cabenuva was first approved, advocates in the community and among public services stressed concern about getting patients to return for monthly shots and the logistics of administering the shots. The concern on costs to public programs also raised its head and has done so even more recently as a limited study concluded Apretude wasn’t “cost-effective”. However, in the time since these initial discussions, tens of millions of people have received their COVID-19 vaccines, which are situated a mere 3 weeks apart and variant development has left many experts expecting the need for annual boosters of the same. The logistics of administering shots have clearly been addressed. As for the “cost-effectiveness” study, the limitation the authors cite is one that’s patently…ridiculous: “Uncertain clinical and economic benefits of averting future transmissions.” We well know the clinical benefits of preventing transmissions means fewer HIV diagnoses, a goal outlined by the United States’ federal government in the Ending the HIV Epidemic initiative, and the economic realities of preventing new transmissions is as apparent in reducing the costs of care associated with stagnant or even rising transmission rates.
The truth is, long-acting anti-retroviral therapies are the next step in innovation at extending effective care to people at risk of acquiring and living with HIV. These advancements will come with a cost that is significantly outweighed by improvements in patient quality of life, retention in care, and reduction in new transmissions. If we aren’t careful in ensuring equitable access to these innovations, existing health disparities will only grow. Barriers to care originating from payer processes, from formulary inclusion to co-pay accumulator programs, should be well-documented by providers and advocates need to be forceful in seeking access to these innovations for all patients, regardless of income or economic status. Policymakers, lawmakers, and regulators need to move quickly to address these barriers. Innovation waits for no one and that which exists in the balance between these interests are people’s quality of life and their very lives.
The Future is Now: Welcome to the Age of Injectables
For years, HIV advocates have anticipated injectable antiretroviral therapies (ART) – often with a level of excitement. I recall listening to robust discussions between advocates and officials in statewide meetings, reviewing candidate treatments, discussing labor and staffing needs for providers, potential regulatory changes needed to ensure programs could cover the actual syringes associated with injectable ART, given state-based restrictions. The excitement extended from a sense of no longer needing daily tablets (pills) in order to maintain adherence and thus an undetectable viral load, extend quality of life for those experiencing barriers to care like homelessness, and otherwise welcome a new age of treatment – if only by new method of delivery.
In late 2019, we seemed on the edge of such an accomplishment. ART focused pharmaceutical manufacturers Glaxo Smith Kline subsidiary, ViiV, and Johnson & Johnson subsidiary, Janssen, had paired up in an effort to provide the world with its first long-acting ART via injection. However, the Food and Drug Administration (FDA) refused to grant the companies an approval for the dual shot regimen of cabotegravir and rilpivirine (together, “Cabenuva”) due to concerns related to “Chemistry Manufacturing and Controls”. Thirteen months later, on January 21, 2021, Janssen and ViiV announced FDA approval of Cabenuva.
ViiV Healthcare understands the transformative nature of Cabenuva and the many “firsts” associated with a provider-administered injectable therapy for HIV. We will be educating HCPs on how to identify appropriate patients who may prefer or benefit from an option other than daily, oral therapy. Two key considerations are that patients agree to the required monthly dosing schedule and understand the importance of adherence to scheduled dosing visits. We also will be helping educate people living with HIV about Cabenuva and these commitments. - ViiV
According to the product monograph, Cabenuva is a dual intramuscular injection protocol (requiring one shot of cabotegravir and one shot of rilpivirine) monthly, administered by a health care provider. Prior to starting the monthly injections, providers should test tolerability via “oral lead-in” via once daily tablets of both cabotegravir and rilpivirine with a meal. If consumers expect to miss a monthly injection by more than 7 days, once daily oral tablets of cabotegravir and rilpivirine may be used to replace the injections for up to two injection cycles (or 2 months). Contraindictions include any known or suspected resistance to either or both drugs and any intolerability of components of either or both drugs. The injections cannot, at this time, be self-administered.
Despite all of the antici…pation and data showing a higher level of satisfaction than with current regimens among trial participants, some advocates are still cautious and concerns remain regarding logistical accessibility. Regarding financial accessibility, ViiV has already launched its patient assistance program for Cabenuva through ViiVConnect. Florida advocates and members of Florida HIV/AIDS Advocacy Network, Ken Barger, Joey Wynn, and David Brakebill, discussed in…spirited detail varying perspectives on rural access.
Wynn advocated for diversifying public funds, if rural health departments couldn’t meet the demand of a once monthly injection protocol, “If a rural health department can’t do a monthly injection [for ART], when they do injections for all sorts of other disease states, they need to give their money to providers who can.” Barger and Brakebill pointed out that for many rural counties, the health department may be the only provider in the area that’s accessible, with a highlight on concern regarding capacity. Wynn suggested the need for investment in better planning and preparation – not just for injectables, but for situations of natural disasters which have been known to disrupt access to medications and care in the state regularly.
When asked about these concerns, ViiV acknowledged the challenges and provided the following commitment to invest in ensuring more equitable access to care: ViiV Healthcare is also dedicated to improving how HIV treatment and care are delivered in the “real-world” environment through our Implementation Science program. One example of this focus is a study evaluating how improvements in transportation and use of digital tools can help get people living with HIV to their healthcare providers on a regular basis, which if successful we’ll look to implement on a broader scale
This week’s HEAL blog wouldn’t have been possible without the coverage of and reporting on treatment developments in this and other therapeutic areas by Liz Highleyman.
Quotes attributed to ViiV Healthcare are direct and were provided by Robin Gaitens, Product Communications Director.