At the Front Line Against AIDS: In the Words of a Researcher

At the Front Line Against AIDS: In the Words of a Researcher

12.11.12 | By

In light of the report we just released highlighting the medicines in development for HIV/AIDS, I thought this interview with a top infectious disease researcher was worth re-posting.

We had the opportunity to sit down with Daria Hazuda, PhD, Merck Vice President and Worldwide Discovery Franchise Head for Infectious Disease. We spoke about her involvement with HIV/AIDS research and about where this research may take us in the future.

How did you get into biopharmaceutical research?

I've always been interested in the science and medical field. My mother had worked for Janssen, a pharmaceutical company. So when I went to school, I always thought I'd go into medicine somehow. I had the idea after I graduated from college that if I went into pharmaceutical science, I could have the potential to impact far more people than if I were a medical doctor in practice. Of course, I never realized that many people who work in the pharmaceutical industry never ultimately discover or develop a drug, so it was a pretty naive perspective. Still, it drove me toward pharmaceutical discovery.

What encouraged you to move into HIV research?

I was always interested in anthropology as a hobby, so I gravitated toward infectious diseases as a way to marry it with science. When I came to Merck, I didn't know much about virology, but thought it was a good way to combine my interests. The job was originally in the field of new herpes drugs, and I did some work in influenza as well. After a few years, in the 1990s, I came to realize that one of the most important viruses was HIV, so I asked if I could be transferred to that group.

It was an interesting time because it was a pivotal point in HIV drug development. The first data had started coming out that suggested we could control virus replication through combination therapies. I started studying HIV in 1994 and in 1996, the first data from protease inhibitors came out at the big international AIDS conference in Vancouver. I remember sitting in the audience as people were saying that they thought this could cure the disease, but there were hints even then that curing AIDS was going to be a longer process - we had made huge progress, but we hadn't fully solved it. Paul Volberding, a well-known AIDS researcher, was there, and he said, "Look at what we're asking patients to do - take handfuls of pills that make them feel sick all of the time. Let's make this a first step and now try to make them feel better." It made me believe there was still a lot of work that needed to get done.

What were some of the breakthrough moments from your work developing Isentress (raltegravir)?

When we first started the integrase inhibitor program, others were studying small molecule inhibitors that worked in vitro, but didn't inhibit virus replications. We took a step back and asked ourselves why those didn't work. We were lucky that we were given the luxury of doing some of the basic work that then allowed us to go back and identify the first inhibitors that worked completely differently - and that really inhibited the virus from replicating. That was the first eureka moment.

The second was that after several years of getting better compounds, we moved to animal testing and saw that we were inhibiting replication in the animal model. It was the first time we'd seen it really work in vivo!

What about your most disappointing moments?

Just a few months into our in vivo studies, when we'd taken a related molecule into HIV-infected patients and saw it working fantastically, toxicology found serious safety issues and we had to discontinue the compound development. It was the biggest disappointment in 20 years because we had come so far and we were so close.

Fortunately, I work with an amazing number of incredibly talented and dedicated people and we worked really hard to figure out the underlying mechanism of what was going wrong with the toxicity. That allowed us to move forward and try another compound, and Isentress was the winner.

How has HIV/AIDS research changed?

There are still a lot of really important things that we need to do. So there is still a significant effort in making better drugs in the classes that we already have with respect to long-term toxicity and convenience. After all, these patients will be on these compounds for their entire lives.

The Holy Grail, of course, is thinking about approaches to eradication or a cure, and there's a lot of momentum around that in the scientific community based on a better understanding of the mechanism by which the virus persists and how and why the immune system remains dysfunctional.

It's an honor to talk to you. Your work is remarkable.

Honestly, it takes an army. Without hundreds of people who have specific skills and knowledge and experience, you can't bring any drug to market. It takes a large team and a lot of time and effort.

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