Electron microscope image of HIV virions.
Electron microscope image of HIV virions. The virus has the ability to mutate and become resistant to medication. Image courtesy US Centers for Disease Control and Prevention.

The Triangle has been a powerhouse for HIV research, a trend that shows no sign of abating.

By Stephanie Soucheray

If the first month of the new year is any indication, 2014 will be a big year for HIV research in the Triangle.

For the last three decades, Duke University, the University of North Carolina-Chapel Hill and several Triangle public health organizations have made breakthroughs in the understanding, treatment and prevention of HIV. And now, newly published research from UNC shows scientists are one step closer to a cure, while Duke researchers now have the first human HIV vaccine trials slated on the calendar.

J. Victor-Garcia headshot
J. Victor-Garcia. Photo courtesy UNC-Chapel Hill Center for AIDS Research.

“A decade ago, you wouldn’t even think about saying the word ‘cure,’” said J. Victor Garcia, an infectious disease researcher at UNC. “But now the progress being made is tantalizing.”

Garcia was the co-author of a study published earlier this month in PloS Pathogens. The study details a novel combination therapy of antibodies and bacterial toxins that can destroy HIV-infected cells.

It’s a new take on the “kick and kill” theory for curing HIV. Currently, patients with HIV are treated with antiretroviral therapies (ART), cocktails of drugs that reduce the numbers of virus in a patient’s body.

ART can keep the virus out of the blood stream, but the minute therapies are stopped, the virus returns with a vengeance. Researchers, Garcia said, need to find a way to “kick” the virus out of cells where it can lay dormant while patients receive antiretroviral therapies and “kill” the virus so it completely evacuates the patient’s bloodstream.

“We describe the analogy as a guided missile head that finds infected cells,” said Garcia. He and his fellow researchers used mice that have been bred to have an immune system that mimics that of an HIV-infected person.

Despite receiving high doses of ART, HIV persisted in the mice’s cells. It was only when injected with a compound called 3B3-PE38 that HIV was destroyed in the mice’s bodies. Garcia said the antibody component of the compound recognized HIV-infected cells and overwhelmingly allowed the bacteria toxin to destroy the cells.

Now, Garcia said, his work is to find the right “kick” step to match his new killing machine.

“I’m itching to get going with those experiments,” said Garcia. “I have to be careful to find the best possible induction strategies to kick the virus out in patients. We need to try to think outside the box and outsmart [to get] results that eventually translate into a patient’s cure.”

Prevention – not a cure – is at the heart of CHAVI, or Duke’s Center for HIV/AIDS Vaccine Immunology. Earlier this month, CHAVI researchers published a paper in the Proceedings of the National Academy of Sciences. The new research helps create a successful plan for the first HIV human vaccine by identifying what researchers call the “Achilles heel” of the protein coating of HIV, the gp41 membrane proximal external region (MPER). This is the structure that infects healthy cells.

Diagram of the human immunodeficiency virus. The gp-41 MPER is shown in green.
Diagram of the human immunodeficiency virus. The gp-41 MPER is shown in green. Image courtesy U. S. National Institutes of Health.

Barton Haynes, director of the Duke Human Vaccine Institute, said the current work is a road map for vaccine development.

“The virus has sites on its surface that make it vulnerable,” he said. “But it has evolved so that those sites … fool the body’s immune system to think it can’t respond to those sites. We’re now coming up with strategies to get around this.”

Barton F Haynes headshot
Barton Haynes. Photo courtesy Duke University, Human Vaccine Institute.

CHAVI is developing a vaccine composed of a man-made lipid that has a piece of HIV in its outer envelope. Called a lipsome, the vaccine has been tested in mice and rhesus macaques.

“We’re looking at December of 2014 for the first human trials,” said Haynes. He said the trials will most likely be in the United States. “We’ve opened up the black box and now it’s time to really move.”

HIV has killed more than 30 million people worldwide and infected 33 million more. Both Garcia and Haynes said they were hopeful to see a cure and a vaccine in their lifetimes.

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