Novel approach to battling HIV

January 11, 2013

UNT System College of Pharmacy Presents First Peer-Reviewed Paper on Timely Topic

It’s got all the makings of a Hollywood sci-fi blockbuster: earthly defenders unite in a global quest to defeat a heartless, shape-shifting enemy that attacks human DNA.

But this war isn’t fiction. It’s a 30-year-old conflict that’s cost an estimated 35 million lives. The invader is HIV, or human immunodeficiency virus, the cause of AIDS. First reported in 1981, the tiny virus continues to take a giant toll, with an average of more than 2 million new cases reported each year.

Final victory against HIV is still a long way off. But innovative treatment approaches are creating increasingly viable alternatives to what was once a death sentence.

Such an approach appears in the first peer-reviewed paper to come from the new UNT System College of Pharmacy (UNTSCP) at Fort Worth’s UNT Health Science Center. In the publication, author Patrick G. Clay, PharmD, FCCP, CCTI and Professor of Pharmacotherapy, discusses the mechanics of HIV and the study’s innovative strategy to defeat the virus.

Q: Can you briefly summarize where we stand in the battle against HIV and AIDS?

A: Scientists have made amazing strides against HIV. But there are two key elements to understanding this battle. First, regardless of how perfectly a person takes their medicine and treats their body, the virus eventually develops resistance and the drugs no longer work. Second, sometimes patients are infected with a virus strain that doesn’t respond to even the newest and most potent drugs.

Q: What makes the HIV virus so deadly?

A: Let’s make this really simple. Human T-cells or CD4 cells are our body’s "soldiers." They’re responsible for keeping "invaders" or foreign substances like bacteria, fungi and viruses, from making us sick. CD4s normally live about 8 weeks. HIV shortens that to less than 3 days. The body can keep producing new T-cells for up to 5 years on average but then can’t anymore. When this happens, the immune system begins to fail.

Q: How do today’s pharmaceuticals fight the virus?

A: There are nearly 30 anti-HIV drugs that fight the virus in different ways, but for simplicity’s sake, they can be grouped into two main categories: they help prevent the virus from using T-cells to make more copies of itself, or they don’t allow the virus to leave the T-cell and infect other cells. The key thing is they have to be used in combination with 3 or 4 other drugs at the same time. Otherwise, the virus figures out ways to beat the drugs.

Q: So if all this is going on to prevent HIV from replicating, how is it that the virus is still such a problem?

A: The main issue is that the above-mentioned combination therapy only keeps the virus from copying itself to produce more new viruses. The medicines cannot eliminate the virus. This is because the virus’ genetic material has become part of the T-cells’ DNA. At any time, the virus is "hiding" in the T-cell DNA and can emerge again. Another reason it may re-appear is because the medicines were stopped or the virus figured out a way to make copies of itself even though the medicine was present.

Another issue entirely is that the drugs do not get into all the places the virus can hide – like the brain. The virus replicates unchecked there.

Q: What is the innovative approach that you write about?

A: Some time ago, scientists at the University of Washington took a different approach to the battle. Instead of trying to stop the virus from making copies of itself, what if a drug was created that fooled the virus into making changes to its special proteins when it didn’t need to? What if the virus would make so many changes that it could no longer make copies of itself without realizing it? Is this possible? It might be.  

Q: How does this approach work?

A: The approach is called viral decay acceleration. Basically, it means the virus changes, or mutates, its special proteins so much that it can no longer function. KP-1461 is the chemical that may just make this happen. Unfortunately, the research is stalled right now, primarily due to the economic slowdown, which forced researchers to stop the study.

Q: What was your role in this process?

A: My part was to advise on how to design the trial and to serve as lead author for the Phase 1 study and second author on the Phase 2 study publication. The drug made it through Phase 1 testing and entered Phase 2 and is reflected in this peer-reviewed document. Clearly, the concept is promising, but much more work needs to be done.

Q: How would you propose to revive the process?

A: There are some unique characteristics of this chemical that are potential game changers in HIV therapy. These need to be explored to make sure that when we begin testing this drug in people again, we get the best possible answers. To do this takes financing, in the form of venture capital money. When that happens, we can resume the work and perhaps – perhaps – come up with a novel approach to defeating, or at least slowing down, HIV.

 

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