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Dr. Santiago Perez

Finding a true cure: Striving to end the HIV/AIDS epidemic

Marty VandenBroek, MSc Candidate, Translational Medicine

The current challenges and strategies for treating HIV was the topic of discussion at this past week’s Medical Grand Rounds, The Quest for the Holy Grail, presented by Dr. Santiago Perez. Dr. Perez shared the progress made in his studies and those of his peers, as well as his personal expertise from years studying the disease in Mexico, France, and Canada. He followed his presentation with a roundtable discussion with the TMED class to delve further into his experience and what the future holds for HIV treatment.

The current treatment for HIV is antiretroviral therapy (ART), a combination of drugs that are effective at controlling the replication and progression of the virus to manage the disease. This therapy allows patients to live effectively normal lives but is not a true cure. Dr. Perez stressed the importance of finding that cure, despite the effectiveness of ART. He shared discussions with patients who are desperate to be ‘freed’ of the disease. Despite the disease being under control, they still face the stigma of HIV, and even in some countries persecution and imprisonment should they transmit the virus. This leads to a fear of the disease, propagated by societies and media that are uninformed of how well the virus can be managed. Dr. Perez even shared a genuine story highlighting how the most harm to patients is due not to the disease itself, but the social stigma surrounding it.

Two patients have been cured of HIV using haematopoietic stem cell transplantation (HSCT), a therapy that replaces a patient’s immune cells with those from a donor. Both cases involved stem cells with a mutation in CCR5, a receptor that is key to the viral life cycle. However, the mutant CCR5 may not be the key to the cure. Surprisingly, Dr. Perez showed that patients who developed graft versus host disease (GVHD) as a result of HSCT may be cured of HIV, regardless of whether CCR5 was mutated or not. We discussed with Dr. Perez the potential ethical concerns of using GVHD to cure HIV and weighing the risk of inducing GVHD versus other alternatives. The true curative ability of HSCT with GVHD is not yet known, as while these patients appear to be HIV free, they remain on ART as a precaution, as the withdrawal of treatment poses its own risks and ethical concerns.

Other therapies have been trialled in animal models of HIV including gene therapy, which comes with its own ethical concerns should it be applied to humans. In addition, immunotherapies like anti-α4β7 treatment have had varying success, as one study appear to cure every animal, but when the same study was repeated last year not a single animal was cured.

Dr. Perez believed most in the use of CAR T-cell therapy, which allows a patient’s own T cells to be reprogrammed to fight the disease and should minimize the risks to patients. However, further research is required to make this treatment option more effective before being used in humans. This avenue is currently being explored and may only be years away from being applicable to HIV in the clinic.

Regardless of which treatment strategy emerges to cure HIV, Dr. Perez believes with the resources available today, it is possible to end the HIV/AIDS epidemic. By following the 90/90/90 rule, that is that 90% of people with HIV know their status, and 90% of those people receive full ART therapy, and 90% of those individuals have viral suppression, we can change the lives of millions of people worldwide. It requires everyone to be tested for HIV and making policy changes to ensure everyone has accessible ART, both at home and abroad.

At the end of our discussion, Dr. Perez shared his experience travelling the world as part of his research career. He encouraged everyone to explore different cultures, to open your mind and become a better person and researcher. He also shared one skill he thinks everyone should learn for self improvement: cooking. It allows you to take care of yourself, which is of utmost importance, but also teaches you to follow procedures to produce a desired result. Learning to be a good cook means you can adapt and improvise when needed, within limits; you may be able to replace butter with margarine in some cases, but milk and cream are not the same!

It was a pleasure to have Dr. Perez present at grand rounds, and on behalf of the TMED program, thank you for sharing your passion and insights!

 

Comments

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Quentin Tsang

Mon, 01/13/2020 - 13:18

Hi Marty,
This was an excellent summary. I found Dr. Perez's insights on both his expertise in HIV and infectious diseases and his journey to becoming a clinician-scientist to to be captivating.
Perhaps what stuck out to me the most during Grand Rounds and our post-rounds discussion is the impact of the stigma surrounding HIV on patients. While effective therapies exist to control the infection and allow patients to live "normally," the stigma is debilitating, isolating and can cause many mental health co-morbidities, such as depression. Dr. Perez mentions that this stigma may actually deter and prevent the highest risk populations from getting tested and treated for HIV. This causes countless lives lost when their conditions can be controlled.
In Western society, mainly North America and Europe, I believe that the stigma behind HIV is slowly being dismantled. However, in many developing countries, this stigma still plagues patients. As researchers and scientists in health sciences, I believe that we should also be advocates for breaking down the stigma behind HIV (and other conditions) and pioneer initiatives in developing countries to educate the general population about HIV and how the infection can be controlled. This may lead to stigma slowly being dissolved and lead to more at-risk groups getting tested and treated, and hopefully, obtaining the 90/90/90 principle that Dr. Perez says is key.

Name
Quentin Tsang

Good points Quentin!
In doing my own research on stigma and HIV, I found an excellent website that provides global information on HIV/AIDs, with an entire pagethat focuses on the stigma in HIV and the discrimination those affected can feel. It is an excellent summary and I would encourage everyone to take a look at it to learn to fully realize the stigma and the steps we can take to reduce it.

Link to website: https://www.avert.org/professionals/hiv-social-issues/stigma-discrimina…

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Madison MacKinnon

When looking at the website you found Madison I found it shocking how more countries than not, have laws criminalizing HIV. I found this report (http://www.hivjustice.net/wp-content/uploads/2016/05/AHJ2.final2_.10May…) which makes a strong argument against laws criminalizing HIV as it reinforces the stigma associated with HIV. The report also proposes strategies which use scientific evidence and reason to change policies ending HIV criminalization laws.

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Katie Monteith

Thanks guys, it really underscores how much this problem is one of public health and social norms, and not just the basic science question of stopping the virus!

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Marty VandenBroek

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Sophia Linton

Mon, 01/13/2020 - 14:17

Way to go, Marty, that was a great summary!

The reality is that global funding for HIV research is diminishing, and researchers are dividing themselves into two "camps" concerning how best to allocate that funding.

A) Discover A CURE, no matter how involved or expensive (e.g., CAR-T therapy).

B) Discover ONLY a cure that is explicitly targetted to developing countries (e.g., vaccine-based)

While both options are great examples of translational research, which "camp" do people think should receive the most funding?

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Sophia Linton

Thanks Sophia! It's a tough question, there clearly is pros and cons to each side, but I can't help but think we need to find something that helps as many people as possible, and not just a solution that is feasible for some people.

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Marty VandenBroek

Awesome summary Marty! Sophia's question is indeed a tough one, as is the question of committing funds to the search for a vaccine or a cure when some patients are still unable to access life-saving ART. As you rightly said, we need a solution that saves as many lives as possible. As we discussed during the post rounds session, our best bet for beating HIV may be to adopt a comprehensive approach that integrates 90/90/90 together with the search for a cure, while addressing the issue of social stigma.

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Edwin Ocran

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Daniel Rivera

Mon, 01/13/2020 - 19:57

Thanks for the summary, Marty. I was interested in learning more about the 90/90/90 rule and found out that its origin is from the Joint United Nations Programme on HIV/AIDS (UNAIDS) and came about, formally, in 2014. While the new therapies and real patient successes are intriguing and certainly very impressive considering HIV/AIDs was once considered a death sentence, I think Dr. Perez made a good point that the public health component to eradicating HIV/AIDS is equally important. As you summarized it, it seems quite logical. But upon some digging, I found an article reviewing the challenges associated with attaining this goal. Here it is: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435269/

It lists things like consistent and reliable drug delivery, non-uniform data collection, and continuous monitoring amongst patients to be significant hurdles to achieving disease control and eradication via the 90/90/90 approach. I found this article contextualized the real world challenges with disease control well. Worth a quick read!

Name
Daniel Rivera

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Quentin Tsang

Tue, 01/14/2020 - 13:37

In reply to by Anonymous (not verified)

Hi Daniel,
Thanks for posting that article about challenges with the 90/90/90 rule. I think when we are learning about public health issues, as junior students, we are often taught to be optimistic at tackling epidemics. I think 90/90/90, while an effective strategy in theory, is a prime example of this optimistic way of looking at public health issues. While there is nothing wrong with being optimistic, it is also important to be realistic. Challenges listed in the article such as drug delivery are very real problems that developing countries in Africa face. My concern is whether 90/90/90 is a realistic and attainable goal in our lifetime.

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Quentin Tsang

That is a good summary of the challenges facing the 90/90/90 rule Daniel, I think it should be seen as a list of things to overcome, and not excuses to give up. Quentin is right about the importance of being optimistic vs realistic, but I think it is realistic to achieve 90/90/90 if we use our resources effectively! What are other people's thoughts?

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Marty VandenBroek

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Thalia Hua

Tue, 01/14/2020 - 11:56

Well said Marty! Prior to this discussion, I have heard about CAR T-cell therapy in the context of recognizing cancerous cells, so it was definitely very interesting to hear about how these cells can similarly be used against HIV. I think that the rapid success of HIV treatments over the past 40 years can partly be attributed to the abundance of cancer research completed prior, and demonstrates the value of interdisciplinary research. As with genome editing and CAR-T cell therapy, it is exciting to see where all of this will take us in the next 40 years for both HIV and cancer!

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Thalia Hua

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Reem Alzafiri

Tue, 01/14/2020 - 14:29

Great post Marty. What I enjoyed the most about our discussion with Dr. Perez was not only his humour but the experiences he shared with the stigmatization of HIV and how that stigmatization has affected people close to him. I admire Dr. Perez's passion about his work despite how HIV is viewed in our society today. It truly inspired me, giving me a greater appreciation in research.

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Reem Alzafiri

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Spencer Finn

Wed, 01/15/2020 - 23:37

Hi Marty,

Great post! You summarized the grand round and discussion really well! One interesting thing I noticed during Dr. Perez's discussion was how he talked about he two extremely differing views there are in the HIV research world. He discussed how certain people strongly believe that we should be concentrating our efforts more on the management of HIV, while others , Dr. Perez, believe that we should be focusing on a cure. upon listening to Dr. Perez's reasoning for his standing, I agree that focusing on a cure should still be a goal, but maybe more of a longterm goal until we establish the 90/90/90. What side do you stand on?

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Spencer Finn

Thanks for the question Spencer, I think if we have the diagnostic tools and treatments we should be going for 90/90/90. It helps a huge number of people that need medical treatment manage their disease. If we look for a perfect cure we'll still need to implement that when it comes; at some point you need to bite the bullet so to say, and mobilize resources to help people. Anyone else have other thoughts on this?

Name
Marty VandenBroek

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