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poslink Issue 102, Autumn 2023

THE CURE

Talking about HIV cure is complicated. But if our communities are to be prepared for advances – and one day, a cure – it’s important to have the conversation.

Craig Burnett breaks down the different strategies for cure and what it means for people living with HIV. Kirsty Machon considers how to design more inclusive cure research for women. While Jillian Lau provides updates on three clinical trials currently underway at the Alfred Hospital and Gordon Campbell shares insights from five men who participated in a treatment interruption trial.

Featured artworks are by The Huxleys from their 2023 series, Bloodlines, paying homage to legendary LGBTIQ+ artists lost HIV and AIDS.

Why we need to talk about an HIV cure

by Craig Burnett

Senior Research and Policy Officer at Living Positive Victoria

The conversation about HIV cure often swings wildly between being overly sensational to underplaying the advances we have made.

Many people follow the line that the cure is five years away and this is often said anytime there is a new advancement or unexpected result in a study. The cure for HIV has been five years away for the last 30-odd years and this has made many people disengage with the science of HIV cure as it brings false hope. At some point in time, the cure is actually going to be five years away. So how can we recognise that time and how do we prepare for it? The reality is that we have cured HIV, but not in a way which we can roll it out to everyone in a safe and effective way.

The Berlin patient, Timothy Brown, was the first person to be cured through medical intervention.

He was given a stem cell transplant as part of his cancer treatment. The stem cells he was given would completely rebuild his immune system from cells that were immune to the HIV virus. This process has been used on others, including: the London patient, Adam Castillejo; the Düsseldorf patient; and, most recently, the New York patient. The process of curing HIV this way is extremely risky and is not wholly effective. While Timothy Brown’s stem cells were immune from his type of HIV, they were not immune to all HIV strains. Eventually, Timothy got to have the modern-day experience of going on PrEP (Pre-Exposure Prophylaxis) to protect himself from further infection. While this is not thought to necessarily be the same for the other people who are cured, HIV strains can and do adapt.

Most HIV cure research being done at the moment is not focused on this process being viable for all people living with HIV. This begs the question: what will the next HIV cure look like? HIV cure research is furthered by the academic drive of trying to find the answer to a question, and what answer you get depends on what question you are asking. Some studies are designed just to find out if their method can cure HIV. While others are trying to find out which method of HIV cure would be most effective for the most people.

The scientific community has made advancements into many different areas of HIV cure, but we are still uncertain as to what the cure process will look like in totality, nor do we know what it will mean for people who would be cured. Will people cured of HIV need to switch out their HIV medications for PrEP to protect them against further infection?

There are many questions left to answer about HIV cure, both scientifically and socially, and there are diligent researchers looking for the answers, but are HIV services and advocacy organisations ready for the cure?

Before Timothy Brown was cured of HIV, he accessed the services available for people living with HIV, however, once he was cured, he was denied access to these services because he was no longer living with HIV. Timothy found this difficult because these services had been a large part of his life and he was expected to live without their support. The HIV community has learnt from this experience and would not respond the same way now. However, there are no current plans for how people who are cured of HIV will fit into the HIV community and its services when a cure is rolled out en masse.

While it is easy to be overly critical of those whose jobs it is to address the issues facing people living with HIV, how much thought is the HIV community giving towards a cure? There are many questions that we, as a community, can come together and discuss to help inform how we would like to see HIV organisations and the scientific community deal with the advent of a new cure. Some of these questions are: How would you like to be cured? Do you want the cure to provide immunity against further HIV infection? How would you like to engage with HIV services once cured? If we start to think about these questions now, we will be in a better place for when the cure is five years away.

Image: David 2022 from The Huxleys Bloodlines Series.

The many ways of participating in HIV cure research

by Jillian Lau

Infectious Diseases Doctor and Researcher, Melbourne

What exactly is HIV cure research?

Every six months or so, media outlets will report on exciting updates in HIV cure from an international HIV/AIDS scientific conference. It might be a new test able to measure hidden HIV particles. Or the results of a cure focussed clinical trial. At almost every major international HIV conference, another case is reported of a person with HIV cured following a stem cell transplant (like Timothy Ray Brown, the Berlin patient). Sometime the news is more sobering – like a study of a new cure drug halted because of unacceptable side effects.

To be realistic, cure science is still many years away from finding a one-shot cure to HIV, something that will mean no more daily pills, worrying about illness or passing on the virus to loved ones. HIV cure clinical studies (studies with human volunteers) are still in the very early phases.

But, every day, scientists are learning more about HIV and how our bodies react to it. They use blood or tissue donated by people living with HIV to conduct ground-breaking experiments. Many of these ground-breaking advances are taking place right here in Melbourne.

In fact, we at the Alfred Hospital in Melbourne have three studies recruiting people right now:

HI-ART

HI-ART is an observational study. This means that while we are collecting blood samples to study in the lab, we aren’t asking volunteers to take any experimental drugs. We are trying to determine if the number of CD4 T-cells (immune cells that are infected by HIV) you have when you start HIV treatment is related to the number of latently infected cells in your body (cells that have HIV genetic material in them and can multiply). If we can prove this, we can simplify how people are screened and selected for future HIV cure studies. About 3 tablespoons of blood are collected as a once-off sample, with optional sample donation in 1 and 2 years’ time.

EC-Leuka

EC-Leuka is a study for elite controllers. These are people with HIV who can keep HIV at low levels in their blood, without having to take any treatments. We still don’t fully understand why an elite controller can do this. In this study, volunteers would complete a procedure called Leukapheresis. During Leukapheresis, volunteers are connected to a machine. This machine takes blood from one vein, filters out white blood cells (which are the type of cells that HIV infects) and returns the blood back into another vein. This is similar to what is done when people donate plasma at the blood bank. The whole process takes about 3-4 hours and is done in a special department at The Alfred Hospital.

NIVO-LD

NIVO-LD is a study to investigate if a single low dose of nivolumab (a drug commonly used to treat lung and skin cancers) can boost HIV defences in the body. This study has two phases. In the first phase, volunteers receive one infusion of nivolumab through an intravenous drip. Blood and tissue samples are collected to see how good the low dose is at getting into the blood and lymph glands. In the second phase, volunteers are allocated at random to either receive the single dose of nivolumab determined most effective in phase 1, or a placebo (an infusion with no active drug in it). Participants in this phase of the study would not know what they are receiving. This is followed by an antiviral treatment interruption to understand what happens to HIV immune responses and control of virus in the absence of HIV antivirals. The treatment interruption is closely monitored, with weekly safety visits for blood tests and reviews with a doctor.

As you can see, not all HIV cure research involves taking experimental drugs and complex studies.

If you’re keen to get involved, but don’t have the time to commit to multiple study visits, there are other ways you can participate. We are looking for volunteers to donate blood or tissue specimens so that our scientists can work their magic in the lab. This may only comprise of 1-3 study visits at a clinic. This would not involve taking experimental medications or a treatment interruption.

Not all HIV cure research involves a needle. We are always running surveys, interviews, and focus groups to understand some of the trickier aspect of achieving an HIV cure. This includes trying to answer questions like:

  • How far away is a cure?
  • Would the cure work for everyone? Would it work for you?
  • Would you be comfortable stopping your regular HIV treatment in a cure trial?
  • How would being in a cure trial impact your health?
  • If a cure is found, how will it be made affordable and accessible to people around the world who need it?

Image: Freddie 2022 from The Huxleys Bloodlines Series.

If you’re interested in hearing more about HIV cure, but not quite sure if you want to enrol in a clinical trial right now, you can still be involved! By signing up to the Victorian HIV cure volunteer database you can indicate what type of studies you would like to be contacted about in the future and sign up to receive a regular emailed newsletter focused on HIV cure updates.

You can read about other current HIV cure research studies here or email clinresearch@alfred.org.au.

Missing Voices: Meaningfully engaging women in HIV cure research

by Kirsty Machon

Executive Officer of Positive Women Victoria

In Australia, women make up 12 per cent of all Australians living with HIV, but their rates of participation in clinical research are much lower.

Does this matter?

Clinicians and researchers say absolutely it does. Medications and vaccines for all sorts of different conditions can be experienced very differently in women’s bodies. They may act differently on women’s bodies as well. For example, women can experience different side effects or more severe side effects when compared with men, and this has been reported for a number of HIV treatments. The efficacy or effects of medications and vaccines can also be affected by things like hormones, body fat distribution, or sex-based differences in the immune system.

In 2019, Positive Women Victoria and the Australian Research Centre in Sex, Health and Society at La Trobe University teamed up on the Missing Voices research project to learn about some of the barriers to women’s participation in HIV clinical trials, with a particular focus on HIV cure research. The research team asked women living with HIV and clinicians involved in recruiting people into HIV clinical trials how women perceived HIV cure research, how engaged they were with the science, and what sorts of things might encourage or discourage them from participating in trials.

Many of the barriers identified were practical in nature.

One practical barrier was how the time needed for clinic visits, blood tests and monitoring could impact on parenting and other family responsibilities. The study also found that the attitudes and beliefs of the doctors recruiting participants into cure trials influenced the participation rate as much as the beliefs or attitudes of the women living with HIV.

The women interviewed gave a number of reasons for being hesitant or not participating in research, including:

  • stigma
  • fear that clinical data may not be secure and HIV status may be exposed
  • lack of knowledge about which research trials were open to recruitment
  • concerns about side effects, safety or the potential impact of experimental medicines on future sexual and reproductive health
  • language barriers.

Some of these practical barriers to research participation could be addressed by making changes to the way trials are designed (minimising site visits, introducing home clinical visits, or using telehealth to reduce the need for travel to a clinic site). But other barriers, like the stigma experienced and faced by so many women living with HIV, may be harder to remove because these issues are far deeper than just the practicalities of trial design.

A significant proportion of women who live with HIV in Australia were born overseas.

Some of the clinicians interviewed said they were reluctant to talk about research trials with women whose first language is not English because they weren’t confident that the women were truly giving informed consent. Clinicians also worried that by discussing trial opportunities with a patient, the patient might think they were recommending or even asking the patient enrol in the study, and that the patient might say ‘yes’ only out of a desire to please their doctor.

The fear of having clinical and health data collected and held by researchers was another reason women said they might be reluctant to enrol in research. Some women said they did not trust that information would be kept secure and felt vulnerable to privacy breaches.

The informed consent processes emerged as especially important for women. Researchers may need to factor in additional time to explain studies if there are language barriers, and to clearly explain how confidential health information gathered in trials is collected, held, used, and protected.

Another important barrier was concern over the potential effects of early-phase or experimental treatments on future reproductive health.

HIV cure research, specifically, presents some unique challenges for recruiting women. The research may involve novel approaches, new agents or complex scientific concepts. Some clinicians talked about the difficulties in describing the aims of studies, or the potential risks or benefits, to their patients, when they themselves find the science complex and daunting.

Many cure trial protocols require participants stop their current HIV treatment in order to assess the effectiveness of the intervention. For many women, maintaining a successful treatment regimen and achieving an undetectable viral load has enormous psychological importance, even more so because it means women can enjoy sex with confidence or without needing to disclose their status.

One other important question raised by the Missing Voices project suggests a need for further discussion in the research community. When we talk of the equitable participation of women in clinical trials, including cure research, what does this really mean in Australia, where the overall numbers of women living with HIV are small? What percentage of female participation would be a reasonable aspiration, and what would help achieve it?

Image: Sylvester 2022 from The Huxleys Bloodlines Series.

Treatment interrupted: Participants' experience of a recent Australian cure study

By Gordon Campbell

Researcher at Swinburne University

Clinical studies investigating potential HIV cures often use treatment interruptions, or carefully monitored pauses in HIV treatment to see if the drug or strategy being tested can control HIV without the need for antivirals.

This article is about a recent study which asked people with HIV about their motivations and experiences of participating in the TITAN Trial.

The TITAN Trial

The TITAN study was conducted by researchers at Aarhus University Hospital in Denmark, and several participants were recruited through The Alfred Hospital and The Doherty Institute in Melbourne. People participating in the trial attended The Alfred for multiple study visits over 6 to 9 months. Some were treated with a combination of drugs designed to neutralise HIV and boost the participant’s own immune system against HIV, while others were treated with a placebo (an injection or infusion with no active drug in it). During the study, participants stopped taking their HIV medications and returned every week to have their virus levels in blood checked. If their virus levels rose above a pre-specified threshold, the researchers recommended that they resume their HIV treatment, which they all did.

I interviewed five people with HIV, all male, while they were active participants in this study. When I spoke with them, they were either in the treatment interruption phase or had resumed HIV treatment because their virus levels had risen to the point where the study doctors had recommended that they go back on antivirals.

The cure trial experience

The participants were motivated to support the HIV community by helping to find a cure. They had an interest in cure science, a curiosity about their own immune system, and were optimistic that eventually clinical trials would lead to improved HIV treatment or cure.

“I am sort of at the older end of the spectrum…. but for those younger ones that are coming through, I guess, whatever I can do to make things easier for them, I guess is positive.”

“So, to go find a study that, you know, possibly has a result of where now I no longer have to take medication every day is great.”

“I’d like to be optimistic… I was reading …the other day where somebody said, why can't we just flush your body of all the blood that you’ve got and put fresh blood back in? … It makes me wonder. Why can’t we do that?”

Because of their trust in and familiarity with The Alfred clinical research team and facilities they did not find the treatment regimen unduly inconvenient or unpleasant.

“And the guys at the Alfred were brilliant. I just said look you know I have a preference for nine o'clock appointment, if you can possibly swing that every, every time we have our appointment, that’s great. And James and Michelle live to accommodate that. So that's been brilliant. The guys in the research centre are amazing.”

The people I spoke to liked the break from having to take HIV treatment daily, both physically and emotionally. Some experienced mild side-effects, but most felt well through the trial. They did not have concerns for their health because of being off treatment. Antiviral treatment was described as central to their lives, and so coming off treatment was very significant to them.

They had hoped to stay off HIV antivirals as long as possible, and were disappointed when their virus levels rebounded and they needed to go back onto treatment. However, they understood and accepted the need to do so.

“So unfortunately for me the test results that I got on Tuesday put me at that point where it was a fourth week over 1000 so therefore the recommendation is you go back on the treatment.”

“I mean you know initially when you start, they're taking a copious amount of bloods, they’re closely monitoring you, letting you know viral loads, CD4 counts each week, blood pressure, heart rate, all those sorts of things every week. So, I feel very comfortable with the staff at the Alfred.”

Participants were grateful for good health, very interested in the health of their bodies, their immune systems and their journey through life off HIV treatment.

“You know you’re relatively healthy, your body’s responding to the ART (HIV antivirals), and you know, whatever combination of drugs you may be on they’re obviously working and able to keep, you know, me at an undetectable level.”

Going forward

We learned that daily antivirals are integral to people’s experience of living well with HIV and that pausing treatment can be confronting. Participants felt positive about their experiences and had a sense of contributing to significant advances in HIV science. Trust in the research team was essential to ensuring participants felt safe, and optimistic, about the trial and advances toward a cure.

The findings from this study will help guide the design of future treatment interruption trials. The positive participant feedback shows that community members are willing to participate in HIV cure studies that interrupt treatment to support HIV community, and they are optimistic about improved HIV treatment and cure.

Image: Leigh 2022 from The Huxleys Bloodlines Series.

Acknowledgements: I would like to thank the participants and my fellow team members, Dr Jillian Lau, Associate Professor Jennifer Power and Associate Professor James McMahon.

Contact: Dr Gordon Campbell, gecampbell@swin.edu.au, PH: 61 3 9214 8422

Cover photo: Keith (2022) from The Huxleys' Bloodlines Series.

Will and Garrett Huxley (Aus/Gumbaynggirr/Yorta Yorta) are Melbourne-based collaborative performance and visual artists. Who work together as The Huxleys.

Bloodlines is multi art form exhibition which honours and worships legendary artists lost to HIV/AIDS. A loving tribute to the many influential voices silenced by the HIV/AIDS epidemic of the 1980s and 90s.

The Huxleys work evokes the colourful rebellious and creative spirit of these queer saints. Outwardly LGBTIQA+ artists that helped shift the worlds of queer art and culture into new realms. The work pays a heartfelt debt to artists who paved the way and informed and inspired the practices of The Huxleys and countless other artists working today.

Utilising their skills of costume design, performance and photography The Huxleys work is designed as a joyous sparkling séance, celebrating queer excellence. Interpreting each artist's influence and oeuvre in a uniquely Huxley fashion.

Poslink is the newsletter of Living Positive Victoria and provides readers with the latest HIV treatment and service information, personal stories of living with HIV and helpful advice on maintaining a healthy lifestyle. Click here to subscribe and read previous issues. Poslink is always seeking writers to share their personal stories or expert advice with our readers. If you are interested in becoming a writer please email info@livingpositivevictoria.org.au

ISSN 1448-7764

Created By
Timothy Krulic
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