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.
Integrating HIV Treatment with Gender-Affirming Care
In our pursuit of health equity, it's critical to focus on the specific needs of transgender people living with HIV, particularly regarding the safe and effective use of antiretroviral therapy (ART) alongside gender-affirming hormone therapy (GAHT). A groundbreaking study conducted by Thomas Jefferson University and the National Institutes of Health (NIH) has significantly advanced our understanding of ART with GAHT for transgender people, specifically women, living with HIV. This research, a direct response to the previously identified gaps in knowledge, offers concrete evidence on the safety of such co-administration, marking a shift in how healthcare providers can approach treatment plans for their transgender patients.
Until now, the apprehension to combine ART and GAHT has led a significant portion of the community to modify their treatment regimens due to fears of adverse interactions. A 2017 study in LGBT Health reveals the depth of this issue, noting that among study participants 40% reported not taking ART (12%), GAHT (12%), or both (16%) as directed due to drug-drug interaction (DDI) concerns. The recent study, published in Clinical and Translational Science, directly addresses these concerns by analyzing the pharmacokinetic interactions of doravirine, tenofovir (key components of ART), and estradiol (a common estrogen used in GAHT). The findings reveal that these medications, when used together, do not significantly impact each other's effectiveness, providing a much-needed evidence base to support the concurrent use of ART and GAHT.
For transgender women living with HIV, the integration of ART and GAHT is essential not only for managing their HIV status but also for affirming their gender identity. This aspect of their healthcare journey underscores the need for clear, evidence-based guidelines that address the co-administration of these treatments without compromising their efficacy or safety. The recent study's findings mark a significant advancement in our understanding, challenging previous assumptions about potential DDIs.
Safety of Co-administration
The study, "Bidirectional pharmacokinetics of doravirine, tenofovir, and feminizing hormones in transgender women (IDentify): A randomized crossover trial," examines the pharmacokinetic parameters—essentially, how the body absorbs, distributes, metabolizes, and excretes a drug—of doravirine and tenofovir (two key antiretroviral medications) when administered alongside estradiol, a common estrogen used in GAHT.
The findings are significant: the co-administration of these ART medications with estradiol does not significantly alter the effectiveness of each drug. Specifically, the study observed that the levels of doravirine, tenofovir, and estradiol remained stable when used together, indicating that these medications can be safely combined without diminishing their ability to treat HIV or support gender transition.
This research addresses a critical gap in healthcare for transgender women living with HIV, who have historically faced uncertainty about combining ART with GAHT. By demonstrating that these medications do not interfere with one another to a clinically significant degree, the study reassures patients and healthcare providers alike that pursuing both HIV treatment and gender affirmation simultaneously is both safe and viable.
Furthermore, this study lays the groundwork for more informed healthcare practices. It underscores the importance of considering the unique needs of transgender people in HIV treatment plans and encourages ongoing research to explore the interactions between various ART and GAHT regimens. Ultimately, this evidence supports the development of comprehensive care models that fully address the health and well-being of transgender women living with HIV, ensuring they receive effective, affirming care without compromise.
Advancing Guidelines and Communication for Integrated Care
For providers, this new data addresses the concerns expressed in a prior literature review in the Journal of the International AIDS Society, which noted the "insufficient data to address DDIs between ART and feminizing hormone regimens." Now, with fresh insights available, the emphasis can shift to using this updated information to craft and apply comprehensive guidelines and to kickstart education campaigns for providers and the community that align with these new findings.
The urgency now is to convert this research into practical, accessible guidelines that assist healthcare providers and transgender women in navigating the safe use of ART alongside GAHT. It's critical to update healthcare providers with the latest evidence, ensuring they are well-equipped to guide their patients through informed treatment choices. This means integrating new research findings into professional development programs and encouraging open, knowledgeable conversations between healthcare professionals and their patients about the combined use of these treatments.
Expanding the Scope: Inclusive Research for Transgender Men and Non-Binary People
While significant strides have been made in understanding the co-administration of antiretroviral therapy (ART) and gender-affirming hormone therapy (GAHT) for transgender women, our knowledge remains limited when it comes to transgender men and non-binary people living with HIV and seeking gender affirming care. With the completion of this major study by Thomas Jefferson University and the NIH, the next step is to expand our research efforts to encompass the full spectrum of transgender experiences, ensuring that future studies are as inclusive and comprehensive as possible.
Transgender men and non-binary people face unique healthcare challenges that are often overlooked in medical research. This oversight not only perpetuates health disparities but also leaves significant gaps in our understanding of how ART interacts with testosterone and other aspects of gender-affirming care utilized by transgender men and non-binary people. To ensure that all members of the transgender community receive comprehensive and affirming care, it is imperative that future studies specifically investigate these interactions.
The call for research extends beyond the pharmacokinetic interactions to encompass the physiological, psychological, and social outcomes of combining HIV treatment with gender-affirming care across all gender identities. Such studies should aim to provide a holistic understanding of treatment efficacy, safety, and the overall well-being of gender diverse patients, regardless of their specific gender identity or the nature of their gender-affirming treatments.
By advocating for and conducting research that includes transgender men and non-binary people, we can move towards a healthcare model that truly embraces diversity and inclusivity. This approach not only enriches our collective knowledge but also ensures that healthcare practices and guidelines are reflective of the needs of the entire transgender community. It is through this comprehensive understanding that we can improve care, enhance treatment adherence, and ultimately support the health and well-being of all transgender people living with HIV.
Mobilizing for Inclusive Healthcare Reform
The recent advancements in understanding the co-administration of antiretroviral therapy (ART) and gender-affirming hormone therapy (GAHT) represent a significant step forward. However, the journey towards fully supporting the health and well-being of all transgender people living with HIV continues. We must intensify our efforts in advocacy, education, and policy reform to ensure equitable treatment for everyone. Here's how different stakeholders can contribute:
For Healthcare Providers:
Educate Yourself: Actively seek out and participate in continuing medical education (CME) opportunities focused on the latest research in ART and GAHT co-administration. Utilize resources from reputable organizations such as the World Professional Association for Transgender Health (WPATH) and the Centers for Disease Control and Prevention (CDC).
Practice Inclusive Care: Implement guidelines and practices in your clinical setting that respect and address the unique needs of transgender patients. Ensure that your staff is trained in cultural competency regarding transgender health issues.
For Researchers:
Fill the Research Gaps: Prioritize studies that explore the long-term health implications of ART and GAHT co-administration, especially for underrepresented groups within the transgender community, such as transgender men and non-binary people.
Collaborate with the Community: Engage with transgender communities to ensure that research is inclusive, relevant, and respectful. Consider community-based participatory research (CBPR) approaches to involve community members in the research process.
For Policymakers:
Develop Evidence-Based Guidelines: Work with medical experts and advocates to create and enforce guidelines that facilitate the safe co-administration of HIV medications and gender-affirming therapies. These guidelines should be based on the latest research and best practices.
Support Access to Care: Advocate for policies that remove barriers to accessing both HIV treatment and gender-affirming care. This includes ensuring coverage by insurance providers and addressing legal and systemic obstacles that transgender people face.
For Advocates and Community Leaders:
Raise Awareness: Use your platforms to disseminate accurate information about the safety and importance of integrating ART with GAHT. Highlight stories and data that underscore the positive impact of affirming care.
Mobilize Support: Organize campaigns to advocate for improved healthcare policies, increased research funding, and greater awareness of transgender health needs. Collaborate with healthcare providers, researchers, and policymakers to amplify your efforts.
Together, we can bridge the gaps in care and knowledge, creating a future where every transgender person living with HIV has access to the treatments they need, free from stigma and barriers. Let's commit to a healthcare environment that celebrates diversity, champions inclusivity, and ensures comprehensive care for all.
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.