The breaking science from IAS 2023

In this episode of HIV unmuted, the award-winning IAS podcast, we take a deep dive into the breaking science being released at IAS 2023 and explain why these breakthroughs are so important for people living with and affected by HIV.   

Set in Australia, a country that is closing in on the elimination of HIV transmission, the conference highlights the latest research, including more hope for an HIV cure, expanding prevention options and insights into mpox. Guests also give us insight into exciting studies on prevention strategies for cardiovascular disease and post-treatment control of HIV in children who are treated early on.   

These studies move us in the right direction. Yet, as our last guest makes clear, scientific advances alone can only get us so far. We must address persisting inequalities that remain in the HIV response. And we must put people first.   

Meet our guests: 

• Gracia Violeta Ross Quiroga, Programme Executive at the World Council of Churches, describes the potential life-changing impact the cutting-edge research has on herself and other people living with HIV. She tells us what it was like to grow up in a conservative Bolivia in the early 2000s without access to life-saving HIV treatment. 
• Sharon Lewin, IAS President, IAS 2023 International Co-Chair and Director of the Peter Doherty Institute for Infection and Immunity, helps us understand the scientific significance of the breaking science.   
• James Ward, a Pitjantjatjara and Nukunu man, who is also an infectious diseases epidemiologist and the Director of the Poche Centre for Indigenous Health at the University of Queensland, tells us why the latest science doesn't always reach vulnerable communities. 

Transcript

Femi Oke:
Welcome to HIV Unmuted, the IAS International AIDS Societies podcast. I'm your host, Femi K. We're here at the 12th IAS conference on HIV science, also known as IAS 2023 taking place in Brisbane, Australia and virtually set in a country that is closing in on the elimination of HIV transmission. This conference presents the latest HIV research and moves science into practice.

News:
Last year, Australia recorded its lowest number of new HIV diagnoses since 1984. The country's AIDS organizations now aim to end transmission altogether on our shores by the end of the decade. It's what they call virtual elimination.

Femi Oke:
In this episode, our guests walk us through the cutting edge science from IAS 2023 and explain why these breakthroughs are so important for people living with and affected by HIV. Highlights of the breaking science include more hope for an HIV cure, expanding prevention options and data on O x. We also touch on exciting studies on prevention strategies for cardiovascular disease and post-treatment control of HIV in children who are treated early on. Sharon Lewin, IAS president, IAS 2023 conference co-chair and director of the Peter Doherty Institute for Infection and Immunity helps us understand the scientific significance of the latest research. Later in the episode, we speak to James Ward, APIC Jam, Jack Jara and Kunu man who is also an infectious diseases epidemiologist from the University of Queensland. He tells us why the latest science doesn't always reach vulnerable communities. But first we talk with Gracia Violeta Ross queer oga program executive at the World Council of Churches. She describes the potential life-changing impact this breaking science has on herself and other people living with HIV. She tells us what it was like to grow up in a conservative Bolivia in the early two thousands without access to life-saving HIV treatment.

Gracia Violeta Ross Quiroga:
I was the daughter of an evangelical pastor in a conservative Bolivia. My HIV test was totally unexpected because I didn't feel I was at risk of HIV, but I had an experience of rape two years before my test and two men, uh, raped me on the street. So I think probably they transmitted me HIV you know, it was a big news in 2000 that the daughter of the pastor had aids. Remember those times we could not make the difference between AIDS and HIV people didn't make this difference, so it was aids I was thinking they will ask my father to to leave the leadership. It was a terrible thing to be living with HIV in a country that didn't have any idea of what to do about HIV. There was a lot of stigma. I really felt I was going to die in the next three months, but when my parents accepted me and also when the church said, it's not a problem that you live with HIV, we are going to be with you. That's the moment that I decided to leave to the fullest, even if it was one month or three years.

Femi Oke:
23 years later, GRACIA is now a featured speaker at IAS 2023 gracia. As a person living with HIV, could you tell us what you think is the most exciting science from the conference?

Gracia Violeta Ross Quiroga:
The science of is 2023 that excited me the most is the abstract that were presented uh, towards the cure for HIV I wait to see the day that I benefit from this science.

Femi Oke:
Who better to explain this exciting cure research than world-leading HIV cure expert Sharon Lewin. Sharon, can you tell us more about the late breaking cure science at the conference

Sharon Lewin:
In this case described at I S 2023. Again, it was a person living with HIV who had this type of bone cancer, not a blood cancer, and needed a bone marrow transplant and received a transplant from the donor who was C C five while type. Then the investigators looked for any evidence of virus after the transplant, didn't find any and so he went through what's called a structured treatment interruption, meaning stopping antiviral therapy under post observation and the virus hasn't come back for 18 months.

Femi Oke:
We have heard of cure cases before. Why is this unusual?

Sharon Lewin:
There are now six cases of people who have been cured after receiving a bone marrow transplant from a donna who's naturally resistant to HIV V. So about 5% of Caucasians are naturally resistant to HIV because they lack the receptor that HIV needs to get inside the cells like a lock and key and if you don't have the right lock and key fit, the virus can't get in and the lock and key for hiv, something called CCR five and about 5% of people don't have that CCR five gene. This is uh, unusual and it's not the first time people have tried a transplant with a CCR five wild type donor. There were two very famous cases dating back to 2013 that had two people that received these transplants in Boston and they had a period of no viral rebound, but it was short-lived in under six months. The virus was back to this is long lived at 18 months. So lots of further work needed to understand why this person has not rebounded every one of these cure cases, although they are rare give people great hope, particularly people living with hiv.

Femi Oke:
Could you also explain to us about the use of a cancer treatment as a possible HIV cure presented at the conference,

Sharon Lewin:
One of them looked at using a cancer drug called Venetoclax. It's a blockbuster drug for the treatment of a form of leukemia and what Venetoclax does is it it induces suicide in a cell that's dependent on a particular protein that the drug inhibits and some cancers can only survive with this particular survival protein called BCL two and VENITA collapsed blocks BCL two and we've learned that HIV latent infected cells also need BCL two to survive. So we gave Venetoclax into a humanized mouse model on antiretroviral therapy and then we stopped antiretroviral therapy and there was a delay in time to rebound, which is suggestive that the reservoir has been reduced. At the same time, we also collected cells from people living with HIV on antiretroviral therapy and then treated those cells with the same drug venetoclax and found that it indeed killed off infected cells. This was very clear results in both the mouse and what we call ex vivo or out of the body experiments. And

Femi Oke:
What about other innovations in cure Research presented at IAS 2023.

Sharon Lewin:
An interesting approach that our lab has been using is to activate HIV using something called crispr. CRISPR normally cuts, they're like CRISPR's gene scissors and it cuts a gene of interest, but we used CRISPR to activate the gene of interest. We don't have any way to wake up the virus that's truly HIV specific, but CRISPR you can design it to very specifically target the single gene you're after. And in this case we targeted an HIV V gene and woke up the virus. But what's unique about this work is the delivery. We used mRNA wrapped in a fat bubble exactly like an mRNA, Moderna or Pfizer vaccine, but this time we wrapped up mRNA that coded for this CRISPR activation protein and got really good delivery into T-cell lines. I'm very excited about this work cuz it's an HIV specific way to wake up the virus and it uses some pretty cool technology of mRNA to deliver package to a T-cell, which is normally very, very hard to deliver R N a

Femi Oke:
Gracia. What does this research mean for people living with HIV?

Gracia Violeta Ross Quiroga:
We have been waiting for this for a long time, you know, taking treatments for people living with HIV. I think we get used to it but sometimes we also think it's too much. I've been taking these medications for 23 years. I feel very exhausted because in the beginning we used to take whatever was available for us. Some of these medications were very toxic and I can see the effects of these medications are still there even though a long time has passed. So we want more of these science.

Femi Oke:
There is another study presented at IAS 2023, which provides some interesting insights into vertical HIV transmission that might unlock some answers for cure research. Sharon, what can you tell us about the study that followed mother child pairs in South Africa?

Sharon Lewin:
So this is an interesting study that followed about 280 mother child pairs following acquisition of HIV by the child in South Africa. All of the children that were born and had HIV received antiretroviral therapy at birth. The group was followed over time and they made some very interesting observations of the 280 infants that they followed. About 60% of infants that acquired HIV were female, which is more than the likelihood of as a male. When they studied the actual viruses in female and male infants, they found that this molecule that our bodies make when they see something foreign called interferon plays a role in transmission of hiv. What does it directly mean for people living with HIV v? I think this is gonna open up new avenues for early treatments and it also is going to open up new avenues actually around cure, where we're beginning to understand that interferon plays a very important role in viruses that go into hiding and then eventually come out again. So a really kind of, I think quite unexpected findings but actually that do make a lot of biological sense given what we know about the difference between male and female innate immunity.

Femi Oke:
Other breaking science at the conference includes new data on ocs. Sharon, talk us through the findings.

Sharon Lewin:
WHO did a very large study of over 80,000 people with Mpox and found that over half of them also had H hiv. What was surprising was that they found that in people with H HIV who were immunosuppressed, they had a far greater chance of ending up in hospital. I think it's a really good reminder when someone sees a person with m o to think about diagnosing H hiv. We've really gotta make sure HIV is well controlled so people are not immunosuppressed and therefore have adverse outcomes from MPO

Femi Oke:
Garcia, What do other outbreaks like empo mean for people living with affected by H HIV?

Gracia Violeta Ross Quiroga:
Mpox was very complicated because it brought back the stigma quickly. The stigma that we thought we were starting to get people educated about people started to discriminate the stigmatize people living with HIV again for the second time, particularly certain groups like men who have sex with men. So any outbreak that we will have, it will affect us more because it will become like a, like an opportunistic infection. One more that we have to fight, we will have a stigma, we will have this problem with the resources and the priorities at country level.

Femi Oke:
And it's not just other outbreaks that require our attention, but comorbidities too. We know that people living with HIV are more likely to develop cardiovascular disease. Sharon, could you explain to us the findings of the reprieve trial presented at IAS 2023?

Sharon Lewin:
The reprieve studies was a really important clinical trial that will likely have very significant impact on clinical practice IT based, we know that people living with HIV on antiretroviral therapy are at increased risk of poor cardiac outcomes. So reprieve looked at whether a cholesterol reducing drug called pitavastatin given to people that had low to moderate cardiovascular disease risk reduces the chance of a cardiac event. And it was a big study over 7,000 participants in over 12 countries and over a hundred clinical sites. Half the group given pitavastatin, half the group given placebo and actually the study was stopped early by the scientific advisory board because of the benefit pitavastatin had the people in reducing the chance of the cardiac event by 35%, which is really very significant, a very exciting outcome that we really can reduce cardiac events for people living with hiv with primary prevention.

Femi Oke:
Gracia, How does research like this in impact people living with HIV?

Gracia Violeta Ross Quiroga:
This kind of research of the re reprieve study is very important because the health system, uh, is very precarious in most of the developing countries. So they give you the HIV medication, but that's it. They don't know what to do about the problems in bonds in kidneys. So if you as a person living with HIV with cardiovascular problems, you have to seek private healthcare to take care of those and many people cannot afford this. So we need this to be in the country policy with the appropriate funding because sometimes the funding is the reason why they will not implement some of these new developments in science.

Femi Oke:
Ensuring scientific innovations reach the people who need them the most is another key theme at IAS 2023 in this context. Sharon, could you talk us through some of the breaking HIV prevention science?

Sharon Lewin:
There's been major advances in HIV prevention with long acting prep and actually a whole toolbox of ways to reduce, um, the risk of acquiring hiv. The best ACT looked at women's choice around prep and it was a extension study where people were randomized to receive injectable prep, long-acting ca cabotegravir with oral prep Truvada. And 80% of women at the end of that study said they'd rather shape injectable prep. That is a very important finding because injectable prep is still not available in many, many countries, but it was the preferred modality, the ease ability to keep this secret from other family members and partners and a really, you know, telling reminder that prevention modalities that are best determined by people that need them.

Femi Oke:
Gracia, could you talk about why a range of prevention options and personal choice is so important?

Gracia Violeta Ross Quiroga:
In the beginning I used to take 16 pills and it was, uh, it was an issue, you know, because people see you taking medication, they say, what do you have? And you have to decide what you will tell. For some people it's easy to say, you know, these are medications for HIV. For some people it's impossible to say because if you say, you know, next, next, next thing tomorrow is you will be fired from your job. We need to provide women and any other community with a range of options for prevention. People are not living in the same conditions and situations. Uh, there are many differences between CI women, transgender women, women who are doing sex work, women who use drugs, women in all their diversity, and also men in all their diversity. We have to provide a range of options so that people can choose what is best for them.

Femi Oke:
It is vital that people living with and affected by HIV are meaningfully engaged in all scientific research. Our final guest, James Ward, provides a unique perspective on how we can put people first in science.

James Ward:
I'm a Pitjantjatjara Torres Strait man from Central and South Australia. Being both aboriginal and an epidemiologist also enables me to see things with two worlds. It enables me to understand disease burden, its causes and the interventions, but also what impact those interventions may have, especially in terms of feasibility, acceptability, fidelity of those interventions prior to implementation. That's important because often outside researchers don't have that insight to what might be acceptable and feasible in community. And then thirdly, being a part of the community also enables me to yarn informally all the time in social gatherings about what is happening and what do we need to do better. Based

Femi Oke:
On your research on Aboriginal and Torres Strait Islander communities, what can you tell us about the HIV response in Australia?

James Ward:
There are a whole range of things that are inequitable in Australia today, and we've been venturing on this, uh, national initiative called Closing the Gap for the last 15 years are closed gaps that have been created by the ongoing impact of colonization. You know, things like education, housing, employment, um, they all impact on HIV in some way. What we need to do much better is address social determinants of health to improve our likelihood of succeeding. At HIV. We also need to address a few other drivers of HIV. One of 'em is cultural determinants, so beliefs and alternative views about medicine and about disease. Racism is a major issue in Australia, particularly for Aboriginal and Torres Strait Islander people both at the institutional level and systemic racism in the population. We also don't talk often enough about political determinants. So adequate or ineffective funding decisions that impact infectious diseases outcomes for our population. We've got a very long way to go in terms of reaching equity in the whole population.

Femi Oke:
At times, science doesn't reach the communities who need it the most. Can you help us understand the barriers to translating science into practice?

James Ward:
Let me start by saying that we rarely see Aboriginal and Torres Strait Islander people included in clinical trials in Australia. If they're not included in clinical trials, there may be important, either subtle or otherwise differences in how a group may respond to those trial outcomes. And I think this is what the role of research really has to address. So for us in Australia, the people at the edges of HIV v the people who are still been diagnosed, there are still some gay men. There are are people who are injecting drugs, but Aboriginal and Torres Strait Islander people are acquiring HIV. It's still at a rate which is unacceptable and higher than the non-Aboriginal population. We have to tidy up around the edges and ensure people who are falling through the cracks are prioritized and this equity approach really has to be applied.

Femi Oke:
The exciting studies presented at IAS 2023, including developments towards a cure, innovation in prevention and lessons learned from other outbreaks move us in the right direction. Yet scientific advances alone can only get us so far. We must address persisting in inequalities that remain in the HIV response and we must put people first,

Gracia Violeta Ross Quiroga:
So people living with HIV and those at risk should be in the center of this science that is going to develop because we can also take the the torch until we get the policies and the funding.

Femi Oke:
Join us at IAS 2023 from the 23rd to the 26th of July, virtually or in person in Brisbane. If you're listening after July, 2023, catch up on the latest scientific advances by visiting our website. This special conference episode was made possible by the support of ViiV Healthcare. Here is their message.

ViiV Promo:
We won't stop until ambition becomes success,
And the impossible becomes achievable,
Until our research offers more ways to treat, prevent, and hopefully one day cure. HIV because we are ViiV Healthcare here until HIV and AIDS are not.

Femi Oke:
Thank you ViiV Healthcare. I'm Femi oke for the IAS International AIDS Society's podcast, HIV unmuted and you can't keep us quiet.