Arriving in the United States as a young immigrant from Venezuela in 1984, I bore not only aspirations for a brighter future but also the overwhelming fear of a virus that I heard about in the news as soon as I arrived. Months later, I was told I was one of those stricken by this terminal disease. My subsequent years were marked by a triple struggle: getting information to save my life during years before the Internet, caring for and burying my sick friends abandoned by their families, and keeping my HIV status hidden to avoid discrimination from employers. Now, after living with HIV for over 37 years, I stand in awe and gratitude. I have witnessed the incredible advancements in medicine and the unwavering commitment of countless individuals working relentlessly to halt a pandemic that has killed my friends and over 40 million people globally.
Surviving for over 37 years with HIV comes with an entire universe of experiences. For me, my journey began when there was much ignorance and stigma surrounding the virus. We were all terrified of being fired from our jobs, rejected by our families, and being the next ones to die. We could only rely on our community and the few clinicians who had the courage to treat us. Over the years, I have seen and lived through a multitude of challenges and breakthroughs in the fight against HIV and AIDS. I volunteered as an HIV activist and for several clinical studies, resulting in the approval of many HIV medications. However, the aftermath left me with multi-drug resistance (MDR) and a persistent immunological impairment (they call us immunological non-responders or INRs). My CD4 T cells remain below 300 cells/mL, a stark reminder of an immune system that never truly recovered. I am one of those aging MDR-INR long-term survivors. But I am still here, and I am still hopeful to be alive for the cure.
My journey has not been just about numbers or clinical terminologies. It has been about enduring lymphoma, grappling with chronic pain, frequent gastrointestinal issues, chronic fatigue, and the devastating loss of function in my right hand due to Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). These experiences, my participation in clinical research studies, and activism make me uniquely positioned to discuss the current state and future of HIV cure-related research, a topic I am deeply passionate about.
I firmly believe that when conventional methods fail, we must be proactive in seeking alternative solutions to save our lives. I take pride in my pioneering efforts, utilizing approved hormone therapies to combat wasting syndrome for both me and many others, even when we were told in the 1980s and early 1990s that no solutions existed. Continually assessing the risk-to-benefit ratio remains a persistent challenge as we navigate this illness. Simultaneously, we contribute to propelling research forward, either as advocates or as volunteers in clinical studies.
I am a true believer that the community of people with HIV must do whatever it takes to support the altruism of so many unsung heroes who are tirelessly working on each piece of the complex puzzle that is a potential cure for HIV.
An ode to the unsung heroes: HIV researchers
To all past and current HIV researchers: Thank you. Your relentless pursuit of knowledge, innovative approaches, and unwavering commitment have changed the narrative of HIV. Because of you, millions across the globe have regained hope, experienced extended life, and witnessed the transformation of HIV from a death sentence to a chronic, manageable condition.
In my darkest hours, facing the harshest medical challenges, your discoveries and advancements became my lifeline. Each new breakthrough was a beacon of hope, reminding me of the collective strength of humanity in the face of adversity.
Celebrating the milestones: HIV cures and durable antiretroviral treatment (ART)-free control
I am amazed that I am still alive after enduring so much loss of my friends and partners and the health challenges that most of us long-term survivors have overcome. Today, as I write down my experiences and reflections, I am exhilarated by the strides we have made. It filled my heart with hope and joy when I heard about Timothy Brown, the first person cured of HIV. Timothy turned out to become a good friend, so losing him has been difficult not only for me but also for the entire research and patient community. After his loss, hearing that other people have been either cured of HIV or are achieving long-term ART-free control has kept our spirits going. Every single one of these people and their care teams represent a monumental leap in our understanding and our capabilities.
Looking to the horizon: cell and gene therapies
Beyond the present, I am excited about the prospects that I hope to be alive to witness as they become reality. The emerging research on gene therapies and the potential applications of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology [Citation1] could be genuinely groundbreaking. Gene therapies offer a promising avenue for treating HIV by potentially altering the patient’s genetic material to either resist or fight the virus [Citation2]. CRISPR shows promising use in HIV treatment by potentially disrupting the viral DNA integrated in host cells, thus potentially leading to a cure. These are not just scientific techniques; they represent the vanguard of our continued fight against HIV.
Imagine a future where we can manipulate our genetic expressions, harnessing them to offer resilience, immunity, or even a complete cure against HIV. The promise of these treatments, their potential to revolutionize HIV care, and the very notion of turning science fiction into science fact is something that I had only dreamed of when I first got my diagnosis. Yet, here we are, standing on the precipice of such possibilities. As an activist, as a survivor, and as a dreamer, I cannot help but be excited and full of hope about what lies ahead. The challenge will be to make whatever works accessible to over 33 million people living with HIV around the world.
But as we celebrate the successes and milestones about HIV research, there are a few issues that concern me and wish that researchers all over the world helped us change.
The overlooked need for immune boosting therapies
One of the glaring gaps in the current realm of HIV research is the scarcity of efforts directed towards immune-boosting therapies, especially for people like me—living with INR. While there have been monumental strides in antiretroviral therapies that reduce viral loads to undetectable levels, many of us continue to grapple with the consequences of a suppressed immune system. People with INR are at an increased risk of clinical progression to AIDS and non-AIDS events and present higher rates of mortality than people living with HIV and adequate immune reconstitution [Citation3].
I truly believe that any effort to support research groups and sponsors who are looking at boosting functional CD4 cells to help people living with INR will not only help move HIV cure research forward for also help millions of people living with immune deficiencies caused by other diseases. Some of us in the advocacy world have discussed with the U.S. Food and Drugs Administration (FDA) potential ways to encourage research and funding in this area by increasing awareness about patient-related outcomes as part of the approval process for potential therapies for the INR population. The main barrier to proving that increased CD4 cells improve clinical outcomes seems like a logical thing to expect but not as easy as it sounds.
The age exclusion challenge
Another concerning trend in HIV research is the exclusion of people over 65 from participating in HIV cure research [Citation4]. Older adults represent over 50% of the HIV population and, like me, face double jeopardy – the natural aging process coupled with HIV-related complications. By overlooking this demographic, we miss out on crucial data that could inform more tailored interventions for older individuals with HIV.
Missing the personal touch: person-centered research
Most HIV cure research focuses on virological and immunological outcomes. However, these do not paint the complete picture. Patient-reported outcomes [Citation5] related to changes in the quality-of-life post-treatment intervention are crucial. After all, isn’t the overarching goal to ensure people with HIV lead fuller, healthier lives? Understanding the tangible effects of interventions on an individual’s daily life is essential to crafting effective and holistic treatment approaches. We also need more person-centered trial designs that account for the complexity of their lives, and healing-centered trials for people who have suffered past traumas [Citation6]. As we attempt to cure the body, we must not forget the mind.
Lost in translation: complex consent forms
Being a part of numerous clinical studies, I have been handed my fair share of informed consent forms. Often, they are a maze of medical jargon and complex terms to protect researchers and institutions, not to inform the potential participants. More than once, I have felt that these forms were not adequately explained, leaving many volunteers like me feeling overwhelmed and, at times, misinformed. Researchers need to ensure that participants fully comprehend what they are signing up for – a more transparent and comprehensible process is vital. Gladly, some research organizations are now incorporating community advisors that can help in this effort.
The communication gap
The fight against AIDS requires a consolidated effort. Yet, there is a palpable lack of streamlined communication between major entities like the U.S. National Institute of Health (NIH), U.S. FDA, the Department of Health and Human Services (DHHS), and state and local governments. Their combined efforts, driven by a shared vision, can truly accelerate the path to not just managing but curing AIDS for everyone affected or at risk.
The problematic ‘subjects,’ ‘sterilizing’ and ‘target’ terminology
Words matter. Referring to clinical trial volunteers as ‘subjects’ is not just impersonal; it is dehumanizing. We are not passive entities in an experiment; we are active partners in the pursuit of a cure. This terminology needs revisiting, and the HIV community now recommends the use of the Person-First Charter [Citation7]. Identifying us as ‘participants’ or ‘volunteers’ is not only more accurate but also recognizes the invaluable contribution of those who offer themselves in service of medical advancement. Also, we need to be careful with the use of terms related to ‘cure.’ None of us want to be ‘sterilized’ or ‘targeted.’ We also do not want to be compared with non-human primates or mice in HIV conferences. Scientific spaces need to become more patient-friendly, and less stigmatizing and triggering. HIV cure science must also be made more accessible. It is unbelievable that we must continue begging for lay-friendly summaries as part of or following major scientific conferences. Fortunately, we can now use artificial intelligence to convert scientific content to lay-friendly terms, so I hope research teams take advantage of this recent advancement.
Inadequate representation in research
Because of many factors that are a constant discussion between activists, focus groups, regulatory agencies, and research sponsors, clinical research frequently fails to adequately represent people from minoritized background [Citation8] and women [Citation9,Citation10] in the same proportions as they appear in the HIV epidemic. An inclusive approach ensures the findings are applicable across diverse demographics, making treatments more effective for everyone.
In conclusion, while I am deeply grateful for the progress that we have witnessed in the realm of HIV cure-related research, there is much more ground to cover. From understanding the specific needs of diverse demographics to placing an equal emphasis on enhancing the quality of life and mental well-being, our approach needs to be as multifaceted as the challenges we face. As someone who has been at the frontline, both as an activist and someone living with the condition, I urge the research, regulatory, and advocacy community to come together and address these challenges head-on. Only then can we truly aspire for a world free of HIV.
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References
- Hussein M, Molina MA, Berkhout B, et al. A CRISPR-Cas cure for HIV/AIDS. Int J Mol Sci. 2023;24(2):1–15.
- Pauza CD, Huang K, Bordon J. Advances in cell and gene therapy for HIV disease: it is good to be specific. Curr Opin HIV AIDS. 2021;16(2):83–87. https://www.nature.com/articles/s41591-021-01590-5
- Yang S, Su B, Zhang X, et al. Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: challenges of immunological non-responders. J Leukoc Biol. 2020;107(4):597–612.
- Kanazawa J, Gianella S, Concha-Garcia S, et al. Ethical and practical considerations for interventional HIV cure-related research at the end-of-life: a qualitative study with key stakeholders in the United States. BMC Med Ethics. 2021;23(1):2.
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- Dubé K, Perez-Brumer A. Call for justice-informed HIV cure trials with ATIs. Lancet HIV. 2024:1–2; [cited 2024 Jan]. Available from: https://linkinghub.elsevier.com/retrieve/pii/S235230182400002X
- People First Charter; [cited 2024 Feb 19]. Available from: https://peoplefirstcharter.org/.
- Dubé K, Kanazawa JT, Campbell C, et al. Considerations for increasing racial, ethnic, gender and sexual diversity in HIV cure-related research with analytical treatment interruptions: a qualitative inquiry. AIDS Res Hum Retroviruses. 2022;38(1):50–63.
- Namiba A, Kwardem L, Dhairyawan R, et al. From presumptive exclusion towards fair inclusion: perspectives on the involvement of women living with HIV in clinical trials, including stakeholders’ views. Vol 9, Therapeutic advances in infectious disease. SAGE Publications Ltd; 2022. p. 1–17.
- Dubé K, Barr E, Philbin M, et al. Increasing the meaningful involvement of women in HIV cure-related research: a qualitative interview study in the United States. HIV Res Clin Pract. 2023;24(1):2246717.