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The Q&A: Ivan D'Orso

In this week's Q&A, we interview Ivan D’Orso, an assistant professor of microbiology at the University of Texas Southwestern.

Dr. Ivan D'Orso

With each issue, Trib+Health brings you an interview with experts on issues related to health care. Here is this week's subject:

Ivan D’Orso, Ph.D., is an assistant professor in the microbiology department at the University of Texas Southwestern. D’Orso was the senior author of a study that explains how a small protein within HIV manipulates human genes to cause AIDS. His current work focuses on how to use cell biological, biochemical and genetic studies together to eradicate HIV.

Editor's note: This interview has been edited for length and clarity.

Trib+Health: What did you discover during your research? Can you explain it?

Ivan D’Orso: People infected with HIV take a cocktail of antiviral drugs. It stops immune infections, but these compounds do not eradicate HIV from the individual. There’s a big push by NIH (National Institute of Health) to really come up with new strategies to eradicate HIV.

What we know is that instead of vanishing, HIV hides in reservoirs within the body, such as bone marrow, lymph nodes and the brain. … These vitals cannot be eradicated. Because of this there are what we call net needs of the anti-HIV therapies, and basically these are the cause of patients’ increased morbidity and mortality …

My lab works on one particular factor that is called Tat. Tat is a very small protein and is a key factor that plays an important role in controlling the reputation of HIV, transmission and disease prevention. Tat is made early on … but it continues to be expressed under the presence of those anti-HIV drugs or therapies.

Tat can also be released outside infected cells. … By doing that, you can affect multiple processes in the cell. For example, you can cause immune activation. It can deregulate the production of the various immune cell types in the patient. …

What we have done is taken a molecular and biochemical approach to really understand how Tat is really affecting the host, the human cells. We basically identified genes … by which Tat rewires or modulates the infected cell because of this new information we have obtained we can better understand AIDS prevention.

Trib+Health: Why is this so significant?

D’Orso: It is significant because the therapy that has been used for infected individuals, it doesn’t target this protein that I just mentioned — Tat. It was suggested that … by targeting Tat, the immune responses in the host could be restored.

Basically, I worked at providing a basic understanding that is explaining all these immune senses that are being deregulated in infected individuals. Our study suggests that a product targeting Tat will be needed in addition to the current cocktails used to reduce or eliminate cell tissues associated with HIV infection. … This won’t cure the infected individual, but it will … be very beneficial ...

Trib+Health: What is your ultimate goal?

D’Orso: There are two main goals. ... One of our main goals is to elucidate the mechanisms by which these proteins from HIV is affecting targeting immune cells in the host. I just told you that by learning about these mechanisms, we feel like we might be able to help HIV-infected individuals in better ways.

I briefly mentioned the currently known HIV drugs. What they do is pause infection, but they’re not capable of eradicating HIV. Our second goal is to identify new compounds or drugs that are capable of eradicating HIV from the infected individual. What happens is that these patients have to keep taking these cocktail drugs forever.

If we can find new compounds that can reactivate those vitals that remain latent or dormant … in various reservoirs across the body then we might be able to completely eradicate and obtain what is a functional cure.

Trib+Health: How far out is a cure for HIV?

D’Orso: It isn’t clear right now. There are many obstacles we’ve encountered. One of them in the field is knowing that we can activate the size of the reservoir by using potent compounds, but the main problem there is we’re causing a lot of cell toxicity. You can relate it to what happens in chemotherapy and cancer patients.

There has to be a window where we can target, specifically, the HIV-infected cells without affecting normal cells. We haven’t gotten to that point. … We still need to identify compounds that are potent but more selective for the latent cells. It’s unclear how long that will take.

Trib+Health: So this is just a step in the process towards the larger goal of eradicating HIV?

D’Orso: Yes, it is. … The first phase will be to achieve selective potent reactivation in the presence of the antiviral therapy to block new infections. Not only reactive those cells, but also facilitate the immune system to recognize those cells where the vitals have become reactivated.

It’s a complicated two-step process where we need to enthuse those cells out of a dormant state and then the immune system can target those cells. Those are the complications we're facing right now.

Trib+Health: What’s next for you?

D’Orso: We’re really interested in this problem of bringing the dormant or silent HIV back alive. Identifying what the roadblocks are by which we can really achieve high potent and specific reactivations.

We’re working to solve this problem because we believe this is the only solution by which we’re going to find a cure for HIV. … Why? Because if the HIV-infected individuals stop taking their drugs then those dormant viruses become reactivated so this ongoing therapy never stops. It has a lot of secondary effects.

The only way we can cure a patient will be to eliminate every single infected cell in the organism.

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