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HIV cure research doesn’t happen in a bubble. The bodies and lives of people living with HIV are impacted by research. The whole process needs community input and engagement. The INSPIRE project is working to develop new models and educational strategies for encouraging community engagement in HIV cure research.

INSPIRE stands for Improve, Nuture and Strengthen education, collaboration, and communication between People living with HIV and REsearchers. The project aims to influence how these groups work together in HIV cure clinical studies. See here for a more detailed description of the project and its aims.

INSPIRE will have a team on the ground at the International AIDS Society Conference on HIV Science in Mexico City from 21-24 July 2019 (IAS 2019). The team will be hosting pop-up classes on community engagement, and providing snapshot reflections of their experiences.

We will be providing regular updates on the INSPIRE project right here, so watch this space!

What are pop-up classes?

HIV pop-up classes were introduced at AIDS 2018 in Amsterdam. Sponsored by the International Council of AIDS Service Organisations (ICASO), the classes are an innovative strategy for community (and other!) delegates to explore the basics of various essential sciences underpinning the conference content.

Using only a banner to set the stage, presenters facilitate 10-15 mins of accessible scientific content, without scheduling, across the conference venue.

What’s the focus for pop-up classes at IAS2019?

A pop-up class on HIV cure and community partnerships will run up to three times per day during IAS 2019.

This class will explore key strategies for community engagement and its value to basic science, translational science, and those undertaking it. The class is aimed to be provocative and to stimulate discussion. Questions that will be discussed include:

  • What is the HIV community and who is a stakeholder in it?
  • What say should the community have over studies, and when?
  • What are the benefits of heightened community education about HIV cure research on future studies?
  • How can we establish a mutual understanding of both community and research concerns?

The aim is to INSPIRE scientists to consider how community engagement can be improved in the research they perform. We will stimulate the co-creation of innovative strategies during the class as well as discuss strategies that arose from the INSPIRE workshop, with particular emphasis on the role of social media. Ultimately, this class will foster a dialogue amongst scientists and community members attending IAS 2019. This dialogue can then be shared with peers and colleagues, and implemented by class participants.

 Meet the pop-up class instructors Paula Cevaal

Paula has recently returned to the Peter Doherty Institute for Infection and Immunity to undertake a PhD on HIV cure in Professor Sharon Lewin’s lab. While trained as a basic scientist, she submerged herself in community activism after graduating from her Masters degree. She vice-chaired the Amsterdam Youth Force in the lead up to and during AIDS 2018, advocating for meaningful youth participation in the global HIV response.

Jared Stern

Jared is undertaking a PhD in the Peter Doherty Institute for Infection and Immunity after completing a Bachelor of Biomedicine (Honours) at The University of Melbourne. His current research has examined how HIV latency is maintained, revealing novel mechanisms and interactions with host cells to pursue in exploiting as an HIV cure strategy. Jared is a peer facilitator for Gen Next, a youth support group for people living with HIV at Living Positive Victoria, a community-based organisation working to enable and empower people affected by and living with HIV.

The post INSPIRE: new directions in community engagement appeared first on HIV Cure.

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HIV Cure by Doherty Institute - 3w ago

Keystone symposia bring together focused groups of scientists to discuss unpublished research. They provide insights into the current thinking around scientific topics. This year’s Keystone symposium ‘Functional Cures and the Eradication of HIV’ took place in late March. We spoke to Kirby Institute researcher, Chantelle Ahlenstiel to find out what caught her attention.

Can latent HIV be re-activated?

The presentation from San Francisco researcher Eric Verdin triggered a lot of discussion. He explored the differences between latent cells that are and are not responsive to latency reversing agents. His group looked at where HIV inserts itself into host DNA (integration sites), and the DNA structures (chromatin modifications) surrounding the inserted HIV. Both these factors influence whether the inserted HIV can replicate again after a period of latency. Verdin’s results demonstrated that most cells with latent HIV can’t be reactivated. This doesn’t bode well for the use of latency-reversal approaches alone as an HIV cure strategy.

Advances in permanent HIV silencing

A few presenters focused on the ‘block and lock’ approach to HIV cure. ‘Block and lock’ is a strategy to push HIV into ‘deep latency’ where it cannot be re-activated. There have already been some proof-of-concept studies in cell lines and mouse models. Didehydro-Corticostatin A (dCA) is one compound that has been studied.

Dr Susana Valente from the Scripps Research Institute in Florida presented further work on dCA. She described in more detail how it works, and provided further evidence for its use in blocking HIV. Dr Ahlenstiel herself presented evidence on using the PromA molecule to silence HIV in mouse models of both acute and chronic HIV. Fabio Romerio from the University of Maryland presented data on a small by-product of HIV infection called the antisense transcript (Ast). He described how Ast encourages HIV latency through changing the DNA structures around the virus (epigenetic changes).

Other approaches to HIV cure

Despite the big question about whether latent HIV can be reactivated, new latency reversing agents (LRAs) featured strongly. These included combination approaches with LRAs; vaccines; neutralising antibodies and additional immune-modulating agents such as GS-9620 which we’ve written about previously.

Other presentations addressed gene editing approaches. These included the use of CRISPR/Cas9 and Chimeric Antigen Receptor (CAR) T cells. Scott Kitchen from the University of California, Los Angeles, gave an engaging talk on the development of CAR-T cells targeting HIV-infected cells, which are now progressing towards human clinical trials.

Reflecting on the conference, Dr Ahlenstiel says

There is a huge breadth of work going on around the world to find ways to cure HIV. It won’t be easy, and the take-home message for me is that there is unlikely to ever be a one-size-fits-all solution. Similar to combined ART, an HIV cure is likely to be a combination of cure approaches.

The post Key lessons from Keystone appeared first on HIV Cure.

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In the winter issue of Positive Living we’ve four takeaways from CROI — plus why talk of a cure is premature. In an era of U=U and TasP, we ask: are the long-term survivors the forgotten generation? Meanwhile, David Menadue reviews two films that portray the early days of HIV; Dr Louise returns with What’s Your Problem; and Steve Spencer talks of his journey from PrEP to poz. We’ve tips on how to prevent diabetes, and profile influencer Neil McKellar-Stewart. Plus all the news you may have missed. That, and more, in the latest issue of Positive Living — a digital magazine for people living with and affected by HIV.

 Read it here

The post Read the Winter Issue of Positive Living Here appeared first on HIV Cure.

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HIV integration into the host genome, forming the HIV reservoir, represents the major barrier to HIV eradication. It is not clear, however, how the HIV reservoir changes during long-term antiretroviral therapy (ART). Kevin Einkauf and colleagues have performed the first comprehensive study analyzing the intact integrated HIV virus. Profound changes in the structure and composition of HIV reservoir were found in 3 HIV-infected individuals undergoing suppressive ART for at least 8 years. There was also a selection of deeper viral latency during prolonged ART. In a nutshell, the HIV reservoir responsible for viral rebound enters a more latent state after years of ART.

The post HIV reservoir changes dramatically during prolonged ART appeared first on HIV Cure.

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HIV can infect a cell, remain ‘intact’, and replicate but sometimes the virus becomes defective and can’t do so. Intact viruses are the main problem if people stop treatment because they can reactivate. Telling ‘intact’ HIV apart from ‘defective’ HIV is difficult. Pinzone et al. looked in detail at intact and defective viruses in four HIV+ people over time. Their results suggest that cells with intact virus are more likely to die than those with defective virus. This could be important for targeting the latent reservoir. The implications are still unclear from this small but intriguing study.

The post HIV May Play an Evolutionary Tug-of-War in Infected Cells appeared first on HIV Cure.

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HIV Cure by Doherty Institute - 2M ago

Yale researchers have highlighted the role of APOBEC3A (A3A) in sustaining HIV latency. A3A is typically found in immune cells such as macrophages. The new study shows that A3A is also found in CD4 T cells. Detailed experiments in lab models of HIV latency show that A3A blocks HIV reactivation. A3A binds directly to HIV, then brings in other repressive proteins which alter the DNA structure. These epigenetic changes prevent HIV reactivation. If A3A is found to act in a similar way in HIV infected people, it could form a new target for reversing latency and progressing towards a cure.

Read more

The post New clue about HIV latency maintenance appeared first on HIV Cure.

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HIV Cure by Doherty Institute - 3M ago

Undetectable equals Untransmittable. Three powerful words that have come to symbolise a transformative development in HIV treatment. From the fear and stigma of the early days of the HIV epidemic and through the era of HIV treatment, U=U has the potential to shift perceptions of what it means to live with HIV. For people living with HIV, it is a release from the fear of discrimination and rejection. It gives them confidence to enjoy all the pleasures of healthy sexual relationships, to have children, to live without stigma. For others in the community, it shifts perceptions of HIV as something to fear to a manageable condition like so many others.

What is U=U?

The idea that HIV treatment can prevent HIV transmission has been around for over a decade. Studies from the mid-90s on preventing mothers living with HIV from passing HIV to their babies provided early proof of the concept of treatment as prevention. In 2008, the Swiss Statement asserted that people with well-controlled HIV infection could not sexually transmit HIV to sexual partners. Since then, a number of large studies have proven the claims in the Swiss Statement. The U=U campaign launched in 2016 after the completion of HIV transmission studies where only one partner was living with HIV. These studies (HPTN052, PARTNER, PARTNER2 and Opposites Attract ) followed thousands of heterosexual and homosexual couples and found zero risk of transmitting HIV if the HIV positive partner had a sustained undetectable viral load. The powerful U=U consensus statement outlines the principle that has since been endorsed by nearly 800 organisations around the world.

The U=U message is simple. People living with HIV who take their medication as prescribed and who have an undetectable viral load for at least six months cannot transmit HIV through sexual activities. While this message is powerful and relevant for all people living with HIV and their communities, it has a distinct impact on women*. Reducing stigma is one major and powerful way U=U is transforming perceptions.

Heather Ellis, chair of Positive Women Victoria, says “U=U is a key factor in reducing stigma… it reduces fear in new relationships by giving women the confidence to disclose their status and giving HIV negative partners the confidence to continue. It removes the fear of infection”. After living with HIV for 30 years, Susan Paxton wishes the U=U message was stronger. “I know few women who will speak publicly about living with HIV, because they are still weighed down by the burden of secrecy”. She sees the U=U message as powerful within the HIV community, but not reaching the broader community. The power of U=U lies in spreading the message as widely as possible.

How is U=U different for women*?

Sexual health, pregnancy and breastfeeding need to be addressed in the context of U=U. While U=U can prevent sexual transmission of HIV, it does not prevent pregnancy or other sexually transmitted infections. The sexual and reproductive rights of women* living with HIV need to be strengthened and supported within the context of U=U. Jackie, a young mother living with HIV for 3 ½ years says “it’s amazing to know I can have a potential pregnancy without transmission of HIV to my baby, but I’m really disappointed with the current Australian recommendations on breastfeeding”. The World Health Organisation recommends that mothers living with HIV should exclusively breastfeed their babies for the first six months of life while having ongoing access to antiretroviral treatment. In Australia, women living with HIV are advised NOT to breastfeed because of the small risk of transmission of HIV via breastmilk. The data on the risks of HIV transmission via breastmilk are sketchy, with few studies conducted with breastfeeding mothers on continuous treatment.While U=U is clear about the risks of sexual transmission, more research is needed to define the risks of transmission by routes such as breastfeeding.

How does U=U impact the search for an HIV cure?

Heather Ellis says “the treatments we take that brought about U=U are as good as a cure, but I pray scientists will discover a cure for the millions of people globally who don’t have access to HIV drugs. Without access, many will die from AIDS”. Jackie reflects “with U=U, you can have a normal happy life, but cure is still the end game”. For some, well-controlled HIV is good enough and finding a cure is not important. Susan Paxton plainly states “I don’t expect a cure in my lifetime.”

U=U is so simple, it could affect people’s willingness to participate in cure trials requiring treatment interruption. For Susan, treatment interruption gets a decisive no.  She draws on the terror of AIDS: “I know what a raging viral load means. Many people who’ve been diagnosed more recently than me just don’t know how scary it is to think you’re going to die. I’m just going to keep popping my pills.”

For Heather, the decision to interrupt treatment would be dependent on context. “I would be reluctant to interrupt treatment, probably like many people. I would need a lot of information to feel justified, especially because I don’t experience any side effects of treatment.”

Jackie reflects on the history of research involvement from the HIV community “I think about the people who died. It’s because of them that I’m here. It’s because of them that we have U=U”, but her willingness to participate in research comes with constraints. “I’m in two minds. On one hand, I have a good relationship with my doctor and know I would be closely monitored and looked after. On the other hand, I have many other responsibilities. I’m finally in a stable situation after a lot of upheaval in my life”. U=U raises the stakes for finding an HIV cure because it transforms HIV into a manageable, chronic infection.

I think about the people who died. It’s because of them that I’m here. It’s because of them that we have U=U

Jackie

The search for an HIV cure in the U=U era needs to address a range of community concerns. Women* are under-represented in HIV cure trials. There are underlying differences in HIV infection in women* and men, so cure research should involve both. Cure strategies must work just as well for women* as for men. A number of issues exist around access to research studies, many which are more likely to affect women*. These include work commitments, childcare needs and balancing multiple responsibilities.

The design of study visit schedules and support for study participants should consider these issues. Reflecting on her willingness to participate in research, Jackie says, “I’d be 150% in, but there are questions including ‘can I bring my child with me?’ and ‘will it fit around my work commitments?’”. HIV advocacy organisation ICASO released a community brief addressing U=U for women* in late 2018. The brief draws on the experiences of women* living with HIV around the world and calls for women’s* experiences to inform the messaging around U=U. It draws attention to the need to ensure women’s* sexual rights and self-determination, full reproductive rights and equal access to treatment and care.

The search for an HIV cure must include women*. The search for a cure must also reflect the power of U=U.

*women: inclusive of young women, post-menopausal women, mothers, lesbian and queer women, Aboriginal women, women with disabilities and trans women in all the diversity of geography, sexuality, ethnicity, religion, education, employment and socio-economic status.

Thank you, Susan, Jackie and Heather, for generously providing your time and thoughts.

The post Women and cure in the U=U era appeared first on HIV Cure.

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For over 12 years, Timothy Ray Brown, known as the ‘Berlin Patient’, has been the only person to be cured of HIV infection. At the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, researchers have detailed a new case, known as the ‘London Patient’ who may be the second. The case has also been published in Nature.

This case is exciting because it seems to show that Timothy Ray Brown’s case was not a fluke. But the London Patient is still highly unusual. Even if HIV never returns in the London Patient, it is not a strategy that could be used in the millions of others living with HIV around the world. This case has the potential to teach us more about how HIV persists and where new research should focus.

What happened to the London Patient?

The London Patient had been living with HIV for about ten years when he was diagnosed with a type of blood cancer.

After some difficulties treating his cancer with chemotherapy, doctors performed a stem cell transplant. His transplant came from a closely matched donor who lacked the CCR5 co-receptor for HIV. The London Patient stayed on antiretroviral treatment throughout the transplant process. The transplant was successful, and he stopped his antiretroviral treatment about 16 months afterwards.

At all times since the transplant, his HIV viral load has been undetectable, including during the 18 months off treatment. Since the transplant, no traces of infectious HIV have been found.

How does it compare to the Berlin Patient?

There are a lot of similarities between the two cases, but they are not identical.

Both people had long-term, controlled HIV infection and then contracted blood cancers. The Berlin Patient had Acute Myelogenous Leukaemia, and the London Patient had Hodgkin Lymphoma.

The Berlin Patient had a very harsh conditioning regime to prepare for his transplant. Conditioning prepares the body for transplant – it makes space in the bone marrow and reduces the immune response that might affect it. The conditioning regime was much gentler for the London Patient.

The Berlin Patient received a total of two transplants from the same donor, as he experienced a cancer relapse after the first. The London Patient has only received a single transplant.

Both people experienced mild graft-versus-host disease after transplant. This is a common consequence of bone marrow transplant. If the transplanted cells are not a perfect match to the recipient, they can see the rest of the body as foreign and attack them. Both the Berlin and London Patients experienced mild forms of graft-versus-host disease.

The Berlin Patient stopped treatment for HIV just before his first transplant. It is now over 12 years since then and his HIV has remained undetectable for that whole time. On the other hand, the London Patient continued treatment throughout the transplant process and for over a year afterwards. The London Patient stopped treatment about 18 months ago, and his HIV has remained undetectable since that time.

What does this all mean?

The London Patient is exciting because it shows that the Berlin Patient was not a one-off. It is yet to be seen if the London Patient will continue to have undetectable virus. It is too early to say that this is a cure, but it is definitely a case of long-term remission.

Professor Sharon Lewin, Director of the Peter Doherty Institute for Infection and Immunity, reflects on how we should refer to the London Patient:

Do we say he’s cured, or do we say he’s in remission? Probably remission’s a better word because it’s possible the virus could suddenly come back at some time, and we just haven’t had enough experience with people who can control their virus for such a long time to know if it will pop up within the next few months. I’d say if he stayed with an undetectable viral load for 2 or 3 years we would have greater confidence in calling him cured as we do with Timothy Brown.

Professor Sharon Lewin

The critical question is what does this mean for people living with HIV? In the short term, the answer is not much. Keep taking your prescribed antiretrovirals. Stem cell transplants are risky. They will never be done in people who are otherwise healthy.

In the longer term, the London Patient can help focus research around two issues.

The first is around the role of the CCR5 co-receptor. Both the Berlin and London Patients had remarkable responses to the removal of CCR5 from blood cells. Can a form of gene editing do this in people living with HIV without needing a bone marrow transplant?

The other issue is the potential for immune responses to clear the HIV reservoir. The London Patient experienced mild gut-related graft-versus-host disease which may have helped clear remaining HIV-infected cells.

The London Patient is a significant development, but should be kept in perspective.

See Brent Allan discuss the study with Sharon Lewin here:

Interview with Sharon Lewin - YouTube

See Brent Allan talk to James McMahon about the study here:

Interview with James McMahon - YouTube

The post From Berlin to London: making sense of HIV cure claims appeared first on HIV Cure.

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HIV Cure by Doherty Institute - 4M ago

Yale researchers have highlighted the role of APOBEC3A (A3A) in sustaining HIV latency. A3A is typically found in immune cells such as macrophages. The new study shows that A3A is also found in CD4 T cells. Detailed experiments in lab models of HIV latency show that A3A blocks HIV reactivation. A3A binds directly to HIV, then brings in other repressive proteins which alter the DNA structure. These epigenetic changes prevent HIV reactivation. If A3A is found to act in a similar way in HIV infected people, it could form a new target for reversing latency and progressing towards a cure.

The post New clue about HIV latency maintenance appeared first on HIV Cure.

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What might a functional cure for HIV look like? In a recent study, researchers assumed that HIV reactivation from latency occurs about once per week. They assessed three cure strategies: reducing the HIV reservoir, removing susceptible targets and eliciting immune control. A 1000-fold reservoir reduction would delay viral rebound by 20 years if treatment stopped. Removing susceptible targets may be more effective than reservoir reduction, and a therapeutic vaccine needs to block over 99% of reactivation events to have a sustained impact. Together, the effect size of any cure intervention must be assessed together with its durability and tolerability.

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The post What should a functional cure for HIV aim to do? appeared first on HIV Cure.

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