Are we close to the HIV cure? What we learned at the 2022 Advocacy-for-Cure Academy
2022 Advocacy-for-Cure Academy Fellowship Alumna, Yusuf Hassan Wada from Nigeria has committed himself to advocate for HIV cure research in his community, country and continent at large. He shared highlights from the fellowship and reasons to be optimistic.
Every year, a few young minds from different parts of the world aspire to work at the grassroots to understand and mitigate advocacy and research problems towards an HIV cure. These are made possible jointly through the International AIDS Society (Int. AIDS Society) Towards an HIV cure initiative and AVAC awarding fellowship to talented advocates who are working in the HIV field in resource-limited settings and who are interested in HIV care-related advocacy.
The Advocacy-for-Cure Academy fellowship is an experiential training and capacity development course on HIV cure research advocacy. It is a comprehensive learning program engaged in building capacity towards exploring and understanding of HIV cure research in different populations and settings, including in resource-limited countries. It is also amongst the most aspired fellowship programme on HIV cure, keeping in view its dynamic network, training and learning opportunity that it provides from the best scientists, researchers, and advocates around the world.
The fellowship is designed to develop more change leaders in the HIV space who would translate big scientific concept of HIV cure into language that’s more easily understood. This is needed to strengthen communication and information exchange between researchers and advocates working on HIV cures which are required to create positive, sustainable and lasting change in the awareness and knowledge in the community and to impact on their lives.
This year’s programme discussed the latest advances, opportunities and challenges in HIV cure and provided an opportunity to address the key questions being raised in the HIV-cure research community and participate knowledgeably through sessions between researchers at the forefront and community advocates on HIV cure research.
Keeping hope alive:
Potential therapeutic interventions leading to an HIV cure have been on the timeline with two different visions. Starting with treatment-free viral remission which means that the virus is controlled without the need for ART. Although it’s also called the “functional cure”, but it’s really fallen out of favor in the HIV-cure research community, in particular because it was used to describe the Mississippi baby in 2013 — to rather disastrous effect after her virus rebounded. Replication-competent virus remains but is controlled without ART. Nevertheless, there are cases of people who are described as in remission who do not have any replication-competent virus that the researchers can find. No one has proved yet that people in viral remission can’t transmit. What researchers do know is that their viral replication remains controlled without ART. These vision include combined interventions to bolster the immune system and to reduce the pool of residual viruses in order to stimulate the immune system to fight it. The “HIV controllers are example of this vision of HIV cure. While the other vision of the HIV cure is viral eradication and also called the “sterilizing cure” which means that all replication-competent virus has been completely eradicated. The Berlin patient represent an example of a successful HIV sterilizing cure.
A reason to be optimistic:
Available cure therapy for HIV has been elusive since the Berlin case was announced 14 years ago. In 2007, the Berlin patient named Timothy Ray Brown became the first person living with HIV in the world to be cured after he received his stem cell transplants. He had tested positive for HIV in 1995, and more than a decade after in 2006, he was diagnosed with acute myeloid leukaemia. As part of his treatment for leukemia, Brown benefited from a sterilizing cure by receiving a stem cell transplants from a donor. There was no evidence in his body that his viral load has never rebounded or any virus with the capacity to replicate.
In 2019, a case of a London man named Adam Castillejo and “Dusseldorf patient” was first described at a conference with both of them achieving HIV remission following treatment same as what Brown received. Brown also died in 2020, a year after Adam and Dusseldorf patient has “definitely been cured” of HIV. This comes as an exciting form of evidence to the medical community since no one has ever been cured of HIV after Brown which his success wasn’t one-off. Dusseldorf’s patient was diagnosed with HIV in 2010 and a year after with acute myeloid leukemia. In 2018, he interrupted ART and years after no record of viral rebound. A fourth person was reported to achieve HIV remission at this year Conference on Retroviruses and Opportunitic Infections (CROI) in February. A team of American researchers reported for the first time that they had possibly cured HIV in a woman and consider her at a state of HIV remission. This was possible through a cutting-edge stem cell transplant method with no viral rebound 14 months after stopping treatment at the reported time. Although, this strategy isn’t broadly scalable, cost-effective and safe, but it offers proof of concept for a future HIV cure.
In children, cases of sustained ART-free remission have been reported after early ART initiation. In 2013, researchers also reported at the CROI that a Mississippi baby received ART from 30h to 18 months after birth. Although her treatment occurred earlier, ART was then interrupted by the mother at 18 months. Plasma viremia remains undetectable for more than 20 months after interruptions. A virus rebound was observed at after 37 months off treatment and 46 months of age in 2014. So there was about a year when people thought she was functionally cured. This is one of the main reason why researchers are cautious about proclaiming someone cured of HIV. Differently, in 2007, a South African child was also perinatally infected and received ART for 40 weeks. In 2017, the baby was reported to be able to maintain sustained viremia control and still had no viral rebound at 9.5 years of age without ART.
Loreen Willenberg and the Esperanza patient are example of individuals who had an apparent case of natural HIV cure (elite controllers) and raise hope for science. Loreen Willenberg is documented as the first person whose immune system may have cured her of HIV. She was diagnosed with HIV in 1992 and happens have undetectable viremia even when she had stopped treatment. The “Esperanza patient” is a 31-year-old mother who was dubbed after the town in Argentina where she lives. She was first diagnosed with HIV in 2013 and happens to become the second documented case of natural HIV Cure whose own immune system may have cured her of HIV in 2021. She had an 8 years undetectable viremia with then tests, none detectable. Lessons were also learnt from the elite and post-treatment controllers which means that they may be a model to an effective cure. This shows that no one HIV cure strategy is viable strategy for HIV cure. We need to keep pushing on multiple fronts including gene therapy such as kick and kill approach and therapeutic vaccines.
The new challenge:
While there is continuous search for an HIV cure, it’s important to acknowledge the still present barriers getting in the way in the search and ART treatment for people living with HIV. The only way to cure HIV is to find some way to reach the latent viral reservoir. Measuring the HIV reservoir have become so difficult and a great challenge to finding a cure for HIV. Standard clinical practice has established that the ‘viral reservoir’ rebounds if treatment stops. This means that the ‘reservoir’ HIV cells which comprised of T-cells (the cells are memory cells that are programmed to have long life span) are invisible to the ART, because they are not replicating. The reservoir is generally smaller when ART treatment starts earlier (within days to weeks of infection), which may support cure strategies.
The reservoir is also made up mostly of infected resting memory CD4+ T cells that are very long lived and may be partially maintained by proliferative response to antigens. So if ART is discontinued, when these cells become activated the viral life cycle is completed and virus produced leading to infection of other cells. These cells are the reason we can’t cure HIV with ART alone. This means that they cannot reach the virus hidden in memory (only 1/1,000,000 CD4 cells) or otherwise inactive T-cells. This reservoir poses the biggest challenge to HIV elimination.
So, to test for a cure in trials, participants must stop ART treatment to enable researchers to look for a viral rebound of HIV or know if he’s cure. We won’t also know if we have achieved a sterilizing cure unless we can show beyond a reasonable doubt that there is no replication competent virus left. This brings new questions around the need to make awareness on the short and long term effect this pose on safety. So there is need to design studies which accommodate concerns such as pregnancy and delivery of effective treatments which may need to be tailored to specific sex/gender groups. With the rapid pace of science, this also overemphasize the need for community, advocates and researchers to come together in integrating community centered models in discussing potential benefits.
An issue to watch:
Some scientists have proposed that one way to go away with the challenge face is to force all of the viruses out of the cells by finding a way to activate all of them, and then attacking the active viruses with antiviral drugs and/or an immune response. This is commonly called the ‘kick and kill’ method. Gene and cell editing, immune-based approaches and latency reversing agents are pathways currently being explored in laboratories towards HIV virus elimination in the reservoir.
HIV Cure in the Global South:
If an HIV cure is to have a maximal impact, it must be affordable, deliverable, and acceptable in all countries hit hard by the virus. We must also start to plan to ensure successful delivery to those countries most burdened and delivery must come at speed. Planning for an HIV cure in Africa and other low middle income countries (LMIH) should begin now when research looks promising. We saw inequity with the COVID vaccine and in the AIDS response when millions died because drugs were unaffordable. We can’t let it happen again.
So as advocates, we need to increase awareness around the need for investments, political will and resources to prepare for future cure trials in humans. We also need to intensify awareness and advocacy for more funds to be an investment in HIV Cure Research. We need to leave no one behind so that we can all follow the science. We need to move together as a whole and participate in HIV cure research to know how our story will look when we have a successful option.
My biggest hope is that within the next years or decades, we will be closer to finding an HIV cure. Today, efforts have been made to prevent new infections and more people are now pretty much aware of the existence of HIV/AIDS. People living with HIV are now living a longer, healthier and more fulfilling life thanks to protease inhibitors such as antiretroviral therapy (ARVs). So, an effective HIV response requires community involvement and advocacy in key agenda-setting and policy-making spaces. We need policymakers and government to show leadership by supporting R&D, and facilitating sharing of knowledge between academia, industry, communities and public health.
As Prof. Sharon Lewin say:
“It is time to more firmly plant the need for an HIV cure on the policy agenda. While interventions that lead to a meaningful cure — allowing for people to safely stop antiviral drugs — are at least decades away, we must begin planning for it sooner than later. Once available, we must ensure a cure can be successfully delivered to those countries most burdened by the disease, and delivery must come at speed”
As we step closer to an HIV cure, our focus as advocates is to see we all keep the momentum going in placing communities at the centre of our efforts, confronting inequalities, spreading and advocating for all to #FollowtheScience. A cure will not only benefit people living with HIV but also those who are negative.
And the conversations continue!
Yusuf Hassan Wada is a Nigerian and a 2022 fellow of the Advocacy-For-Cure-Academy, jointly hosted by the International AIDS Society and AVAC. He also serves on the Pediatric Adolescent Virus Eradication - Community Advisory Board (PAVE-CAB) focused on finding a cure for perinatal HIV. He works with Society for Family Health, Nigeria. He can be reached on email@example.com