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The Current State of HIV Cure Research: An Interview With Carl Dieffenbach

July 29, 2016

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You know, the title, I believe, of this symposium is "Cure and How it Relates to Clinical Practice." And at this point, that connection is a bit of a mystery to me. Can you describe why that is included?

It's not my conference. My guess is -- we don't know about this reservoir problem. The reason it came into our consciousness is because people have said, "We can cure this disease with therapy. We hit early, hit hard."

It's incumbent on everybody to get on antiretroviral therapy as soon as they are able. It's better for them in the long term, as a person. [...] And it's better for their partners. Because if you're not infectious, you will not spread the virus.

We did, and we got really good virus suppression. But as soon as you stop therapy, there's rebound. And so it's incumbent on everybody to get on antiretroviral therapy as soon as they are able. It's better for them in the long term, as a person. It protects their immune system, regardless of where they are in their stage of infection. And it's better for their partners. Because if you're not infectious, you will not spread the virus. You also can deal with -- maybe it's easier to deal with -- stigma and all of those things.

But I think we, as a society, we need to grapple with this issue of honoring people who are on therapy and, at the same time, not blaming people who aren't. It's really a balance. And we need to encourage and basically promote healthy behavior. Not shaming. Good health means taking care of yourself, taking care of your HIV, taking care of your community.

That's where I think it matters for your average infectious disease or primary health care provider. They have a responsibility to their patients to keep them happy and healthy by keeping them on therapy.

You mentioned several times in your talk about the limits of current assays. How important is it to these investigations of different cure strategies to develop a more accurate and specific assay?

Fundamentally you have a numbers problem. You have one in a million cells that in your average person contain a replication-competent provirus. In order to see 10 or 100, you have to think about the math. In a billion lymphocytes, CD4+ lymphocytes, you would have a thousand proviruses.

Now, if you needed to reduce the level of provirus in the body by four or five logs -- say, five logs -- you would need to remove 1011 lymphocytes from that person to find the one. It becomes impossible using just standard technology.

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There's going to have to be other biomarkers; nucleic acid is great, but this is the problem. You know what the Visible Human is? The Visible Human was a person who donated his body to science. He was a convicted felon. And when he was executed, they froze his body and they literally planed his body away, photographed it and, essentially, it became this set of images that are on the website of the National Library of Medicine.

So, can we figure out technologies or tools to literally go inside a person safely to find that? Now maybe positron, emission spectroscopy, or some other very cool, very expensive, 21st century machine will allow us to go in and have a molecular probe for proviral DNA and be able to find that one cell somewhere in the body. But it's not as if you have a solid tumor that's easy to see. It's literally spread out in every piece of lymphoid tissue from head to toe. It's completely diffuse.

But how important is that technology to the cure research?

I think what we need to be able to do is demonstrate that we're having an impact on the proviral DNA level. You have to be able to assay it and watch it fall. How far it falls you can determine, if people are willing to undergo structured treatment interruptions. But I think that we're going to continue to get more sophisticated about predicting who is rebounding and when they're rebounding. And maybe there's a little bit of a signal just prior to rebound that allows you to restart therapy.

I think it's going to be a set of clinical assays, as well as a careful following of the patient. But it's going to be unbelievably complicated. We're going to get there, and I would love to have that problem.

I just am very optimistic that, at some point, we will get to a place where we have a cure for some portion of the HIV-infected population and that over time it will improve.

Any parting thoughts that you would want the readers of TheBody.com and TheBodyPRO.com, many of whom are HIV-positive, to know about the state of the art in terms of cure research -- anything that the NIH is doing, anything that you find particularly promising?

I just am very optimistic that, at some point, we will get to a place where we have a cure for some portion of the HIV-infected population and that over time it will improve. I think the analogy, coming back to my main analogy, is that therapy has improved so much. I think we will have similar sets of waves of innovation on cure as we go forward.

Ultimately, the goal is to be able to have it not just for people in Manhattan, but for people in Botswana, people in South Africa, people around the world. Ultimately it has to be safe. It has to be scalable. For now, it's a research question.

This transcript has been lightly edited for clarity.

Sony Salzman is a freelance journalist reporting on health care and medicine, who has won awards in both narrative writing and radio journalism. Follow Salzman on Twitter: @sonysalz.


Copyright © 2016 Remedy Health Media, LLC. All rights reserved.

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This article was provided by TheBodyPRO.com.
 

 

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