By Dr Jillian Lau
Cure update from IAS 2023
Dr Jillian Lau of the Doherty Institute and Alfred Health in Melbourne attended the recent IAS (International AIDS Society) HIV Cure and Immunotherapy preconference in Brisbane. Dr Lau also acted as rapporteur for the preconference, along with Ellen Bowden-Reid, a PhD candidate from the Kirby Institute, Sydney. Dr Lau has kindly compiled this report for NAPWHA to share.
The pre-conference meetings are organised by the IAS ‘Towards an HIV Cure’ initiative, and this year the focus was on strategies that target different components of our immune systems, and how this could help us achieve a cure for HIV.
Immune therapies
The forum began by exploring several immune therapies currently in clinical trials. These included:
- A placebo-controlled study on combination broadly neutralizing antibodies (bNABs) currently wrapping up in the UK (The RIO study).
- A single arm study (no placebo) of 10 people in California, USA looking at combination immune therapies: HIV vaccines, 2 broadly neutralizing antibodies, and a class of drugs called “toll like receptor agonists” that boost immune function.
- Three HIV vaccine studies in Spain.
All the studies measured the time it took for HIV viral load to rebound as their main outcome. Viral Load rebound is how long it takes for HIV viral levels to become detectable during ‘analytical treatment interruptions’, or short treatment breaks with frequent viral load monitoring. This reduces the risk of health issues associated with prolonged detectable viral loads for study participants.
In all the reports available so far from these studies, most participants experienced viral rebound during treatment interruption even when specialised tests detected very low levels of HIV at a cellular level. To date no single therapy has been effective enough to show promise for a cure, so is thought that a potent combination of immunotherapies may be needed to achieve a cure, but we also need these combinations to be safe, and tolerable.
Gene activation
In another exciting update, a new drug and drug delivery strategy was presented from the Doherty Institute in Melbourne. This strategy uses gene activating technology known as CRISPR activation, coupled with a nanoparticle delivery system to act on cells containing HIV more efficiently and potently, while minimising the risk of side effects.
A hopeful vaccine
A study by the University of Hong Kong was also presented, showing promising results for a vaccine using PD-1 antibodies (PD-1) in primates. In long term HIV infection, PD-1 attaches to CD4 cells and reduces their ability to fight infection. An effective vaccine could prevent PD-1 from attaching to CD4 cells, leaving them healthy and functional. These antibodies have been studied a great deal in HIV cure science, including in the NIVO-LD study currently recruiting in Melbourne.
Community input
The day was bookended by inspiring community presentations from Heather Ellis from Positive Women Victoria and Michael Louella from the DARE Collaboratory in the USA who spoke about the importance of the use of appropriate language and communication in HIV cure science. There was also a full woman panel discussion on Community Engagement and Diversified Study Populations in Cure Studies.
The Geneva patient
The major HIV cure study presented during the IAS conference was the case of “The Geneva Patient”. A man in his early 50s, had been living with HIV since the 1990s and had been on HIV treatment since 2005. He was diagnosed with an aggressive type of cancer called sarcoma in 2018 and went on to have a stem cell transplant (summary of the science of stem cell transplants in HIV cure), after standard chemotherapy.
In Europe, the ‘International Collaboration to guide and investigate the potential for HIV cure by Stem Cell Transplantation’ (ICISTEM) project collects data on people living with HIV who receive stem cell transplants for cancer. The Geneva Patient was part of the ICISTEM project, and was monitored carefully after his transplant, and continued during his remission from cancer.
Twenty months after stopping HIV treatment, there was no evidence of HIV in his body. Many different clinical and research measures were used to try and find HIV, and no evidence of HIV replication could be detected. The unique aspect of this case is that this man received stem cells from a donor who does not have a genetic variation that prevents HIV from entering T cells. This is unlike other well-known cases of HIV cure following transplant such as the Timothy Brown and Adam Castillejo who were the Berlin and London patients respectively.
This is exciting because other PLHIV needing stem cell transplants may also be able to achieve similar results with needing to find a donor with this genetic variation. On the other hand, this procedure is extremely risky, and not appropriate for PLHIV who do not need a stem cell transplant for cancer.
This man has also had a complication called chronic graft vs host disease, when donated tissue attacks the body of the transplant recipient. He required medications which heavily suppress his immune system, and it’s not yet known what impact those drugs could have on his ability to suppress HIV.
Finally, stem cell transplants from donors without the variation has been used in treating other PLHIV with cancer, but none of them have been able to suppress HIV levels for as long as the Geneva Patient, so it’s possible that this “HIV remission” may not last.
Nevertheless, this was an important study presented at the conference, and it received a lot of media attention.
Key words
Placebo-controlled trial: this a design of a clinical trial where participants are chosen at random to either receive the investigational agent, or a “dummy” drug that has no effect on the body. Depending on what is being studied, placebos can come in intravenous or injection forms (usually saline) or a tablet (sometimes known as a “sugar pill”)
Broadly neutralizing antibodies (bNABs): these are proteins that can target cells infected with HIV, block virus entry and prevent infection of new cells. They are currently being studied for HIV prevention, treatment and cure.
Analytical treatment interruption: closely monitored pause in HIV treatment in the context of a clinical study. Participants are reviewed as frequently as weekly to watch for any adverse effects, and bloods are taken to check viral load, and CD4 counts.
IAS Cure Reports from other attendees
Kiho Tanaka PhD Candidate Doherty Institute kindly shared this report from the IAS 2023 Young Leaders Program.
I had an amazing opportunity to be part of the 2023 IAS Young Leaders Program where young people from around the world came together to share and discuss various topics related to HIV. Many are leading youth advocacy and community work in their home country. Each session was filled with learning and moments of realisation.
Even though treatment prevents transmission and progression into AIDS, stigma and related adherence issues persist. Challenging social issues that we discussed included the questions: Are reproductive health and rights of women living with HIV addressed adequately? How do we spread the correct information in rural villages where people have different cultures and speak different languages? Is the recruitment of clinical trials performed in an ethical manner? People are interested in the science, but often the information isn’t translated well to the public. Without the help of people, research fails to advance and thus communication is crucial.
The fellow young leaders I met in this program are trying to tackle these issues. Learning what my peers are doing to support and lead the community and their perspectives on various needs and challenges was not only inspirational but also filled me with hope and pride that together we could be the change makers. I’m very grateful for this experience and my aspiration to be able to contribute to HIV cure as a scientist became stronger than ever.
Rory Shepherd is another PhD Candidate from the Doherty Institute who also attended the IAS 2023 Young Leaders Program. Rory has also kindly shared a report.
I had the honour of being selected for the 2023 IAS Young Leaders Program, which brought together advocates, students, health care workers and researchers from around the globe to discuss their experiences and learn from one another.
As a researcher, I’m often siloed away from implementation and those for whom the research serves. The variety of young leaders had unique insights into the barriers in treatment access, stigma, and the perception of cure; many offering detailed explanations which dispute some of the broad claims made by media and politicians.
It’s still a guess when a cure will be found, but none of my peers in the program seemed phased by this, with the greatest driver of discussion being the breaking down of current inequities and correcting misinformation; they stressed the value in researchers being able to effectively translate science to a broad audience, a repeating theme. I hope to take their enthusiasm forward to fuel my work.
Heather Ellis from Positive Women Victoria, Melbourne HIV cure Consortium CAB member kindly shared this report.
Just as protease inhibitors were the groundbreaking science at AIDS1996, the findings of a ‘functional cure’ for HIV in the form of long acting injectables when paired with bNABs (broadly neutralizing antibodies), will always be remembered from IAS2023 HIV Science in Brisbane.
Studies presented showed that long-term HIV suppression without (oral) ART was possible for up to nearly 18 months in some cases. However, these people with HIV, referred to as post-treatment controllers (PTC) could have achieved their status without the aid of this ‘functional cure’.
But just as researchers, clinicians and the community back in 1996, were not, at first, fully convinced about protease inhibitors, the same hesitation appears with this new science behind a functional cure. This is partly, because bNABs don’t work for everyone and more research is needed to have the therapy individualised. There was also excitement about the potential of bNABs in developing a vaccine for HIV and for clearing HIV cells in babies soon after birth in situations where the mother does not have an undetectable viral load.
IAS 2023 will also be remembered for the success of long-acting injectables as treatment and prevention and just how rapidly science is progressing in this field and its benefits for adherence and risk of disclosure.
