Managing hope and expectation: Perspectives on HIV cure

HIV cure. Those two little words elicit such hope, expectation and frustration.  This was the theme that ran through the series of presentations at the HIV and Sexual Health Conference in August 2022 in the session HIV Cure: All in the Mix – Bench, Beside, Community.

Scientific HIV cure update

After an energising global perspective on HIV Cure from current International AIDS Society President, Professor Sharon Lewin, Dr Chantelle Ahlenstiel from the Kirby Institute gave a tour-de-force basic science update. She presented the key scientific challenges for developing an equitable and sustainable HIV cure.

A major focus is on understanding the latent reservoir. Scientists need to figure out the reservoir’s spread through multiple organs and cell types and its vast sequence diversity. Dr Ahlenstiel provided a rundown of some of the cure approaches currently under investigation. These include stem cell transplantation with HIV-resistant donor cells (via CCR5 deletion) and gene-editing (with CRISPR/Cas9) to excise the latent HIV-1. She also referred to the study of latency reversing agents for ‘shock and kill‘ and latency inducing agents for ‘block and lock‘ strategies. While some of these approaches are in small scale clinical trials, all approaches require further investigation.

The view from the clinic

Dr Jill Lau offered the audience an update on recent clinical advances in cure science. There are several strategies currently being trialled, providing an important sense of momentum.

Firstly, Dr Lau drew attention to the fifth case of ‘cure’ by stem cell transplantation – the ‘City of Hope Patient’. As with the other similar cases, this HIV cure occurred in the setting of blood cancer. Transplantation is risky and not appropriate for everyone, but these cases are powerful for showing the possibility of HIV cure. Dr Lau also discussed a new case of ‘Exceptional Post Treatment Control’. Post treatment control describes the ability to keep HIV levels below detection limits without therapy. The need to understand how this happens provides a strong motivation for more basic science research.

Advances in mRNA technology during the COVID-19 pandemic are likely to speed up the development of broadly neutralising antibodies (bNAbs). Dr Lau presented early data showing that bNAbs may lead to long periods of ART-free viral control. Promising research suggests drugs targeting Toll Like Receptors (TLR) may reverse HIV latency and activate immune responses that may ultimately remove HIV from the body.

Combining anti-TLR drugs and bNAbs may boost the killing of infected cells and add to antiviral immune responses. This could provide immune control of HIV without the need for antiviral medications. There are multiple studies underway to test this strategy. The TITAN study is an international trial in people with long-standing, well controlled HIV. Participants take combination anti-TLR and bNAb treatments and then interrupt their treatment under close supervision. A similar study was presented earlier in 2022. In that trial, one patient had undetectable virus for 3.7 years after stopping ART.

Bringing the community back to the centre

After these exceptional updates on cure research; Brent Clifton from NAPWHA provided some hard truths from a community perspective.

Most people don’t have time to take part in experimental science

HIV Community Perspective

In setting the scene, Brent reminded us about the Denver Principles and how “nothing about us without us” applied to the entirety of the research process in HIV cure research. What is often reported, however, far too often misleads, obscures and maintains the veils of expectation and frustration. This leads to a mixed understanding about HIV cure research and the sense that “a cure is somewhat close . . . maybe?”

Breadcrumbs for a cure have been laid everywhere

HIV Community Perspective

By engaging people living with HIV in Australia in a community-based participatory research process, Brent drew out a number of community perspectives that struck a chord with everyone attending – policy makers, scientists, clinicians and community alike.

I believe incredibly smart researchers are passionate about the science of finding a cure.

HIV Community Perspective

Although people living with HIV show a strong willingness to take part in HIV cure research, little is known about what studies are taking place.  Participants spoke about not knowing what engagement might look like and how to get involved, demonstrating a latent scepticism about the real-world value and personal impact.

The strength and possibility of hope

We have the tools to engage community around a HIV cure, let’s use them.

HIV Community Perspective

But what about hope? There is no question that people living with HIV want a cure. It is an open conversation between people living with HIV. Media headlines and focus on exciting new developments generate a crescendo of hope. This is often followed by a let down when the details of the article or study are revealed.

I hope it arrives one day.

HIV Community Perspective

There is an appetite for more knowledge about HIV cure research. We need to be better at engaging community throughout the research process. This is where both scientific and community partners keep the community continuously informed rather than focusing only on ‘breakthrough moments’.  As Brent reminded us, “we all need to share in the small wins towards a cure”.

With thanks to Brent Clifton (Deputy Director, NAPWHA) for access to his slides and the quotes from community perspectives.

About the authors:

Brent Allan is a global community engagement consultant and principal of Qthink Consulting. They are a senior advisor to ASHM, International AIDS Society and the U=U Global Advisory Board.

Scott Ledger is a postdoctoral research fellow at the Kirby Institute

David Griffin is an Infectious Diseases Physician at the Alfred Hospital and PhD candidate at Monash University

basic science clinical trial community cure latent reservoir