AIDS—acquired immunity deficiency syndrome—was named in 1982, at the beginning of the epidemic in the U.S. It was another two years before it was known that human immunodeficiency virus (HIV) was the cause of this strange new disease. Death rates rose steadily and steeply over the next decade. By the mid-1990s, AIDS was the leading cause of death for Americans ages 25 to 44 and more than 250,000 people had died from AIDS or AIDS-related causes.
“Some of our most creative people were taken away from us by this terrible disease,” says Emory synthetic chemist Dennis Liotta. “I became increasingly convinced that I had to do something that would make a difference, even though I didn’t know anything about virology. That was my driving force for getting into it and I never looked back.”
Death rates began to decline after multidrug therapy became widely available. Emory researchers were front and center in the discovery of this therapy.
“At the time, we didn’t know too much about HIV. We didn’t know if it was a respiratory virus, we didn’t know if it would affect us personally. But we worked on it because there was a need and an urgency,” says organic medicinal chemist Raymond Schinazi. “When you’re young, you want to save the world. We took the gamble and it paid off.”
HIV is now a chronic, not fatal, diagnosis, largely due to drugs made from compounds that emerged from Emory labs. More than 90 percent of people in the U.S. who have HIV, and many around the world, take at least one of the drugs invented by Emory researchers Liotta, Schinazi, and Woo-Baeg Choi.
Liotta, Professor of Chemistry and Executive Director of the Emory Institute for Drug Development, and Schinazi, Walters Professor of Pediatrics at Emory and Director of the Laboratory of Biochemical Pharmacology, are still hard at work, developing other novel therapeutic agents and furthering vaccine development.
“This is an incredible example of the impact that academic research can have on people’s lives,” says Todd Sherer, Emory Interim Vice President for Research Administration. “We are very proud that the work by Drs. Liotta, Schinazi and Choi has helped so many people.”
Untold numbers of people around the globe have benefitted from this basic research. Go here to watch the story of how the discovery unfolded, and to see patients whose lives were saved by a dark-horse drug regimen that became the most common HIV treatment in the world. Go here to read the full series of blog interviews with inventors, patients, and others.
From me? I was like, excuse me? I had always been the wife of one person, faithful to my husband, I’m not a gay man, never had a blood transfusion. What happened? How could this have come to our family? We were advised by our obstetrician and different doctors that all of us get tested for HIV. It was a very long, drawn-out process back then. Jeff tested positive for HIV, I tested positive for HIV. Jonathan, my oldest son, was HIV-negative. I was pregnant at the time with our third child, and the fate of our unborn child was unknown at the time. There was a 50-50 chance she would be positive. That was a grief-filled period.
Path to academia: He never deviated from his desire to be a chemist—but he did find it a bit difficult to focus for a few years in college. “I got rejected by most graduate schools so quickly, I didn’t even know post mail could go that fast,” he jokes. CUNY had the foresight to accept him, however, and he was soon back on track. “It never really occurred to me that I would ever be anything other than a professor. I interviewed at some pharmaceutical companies. They were perfectly fine, with smart people. But I wanted to do my research, I wanted to teach,” he says.
My mentor: At Yale, I worked with William Prusoff (“the father of antiviral chemotherapy”), who developed the first drug for herpes of the eye. When I started my career at Emory in 1978, I was working on combination chemotherapy drugs for herpesvirus. Unfortunately, at the time, even for herpes, people didn’t believe in combination therapy for viruses. We already had combinations for TB and cancer, but nobody believed you needed them for viral infections.
University advantage: Being connected to a major research university is an advantage over other drug developing groups when trying to get investors and access to assets. You’ve got the intellectual power of the entire university.
The aha moment!: Out of that experience came the idea of combining drugs. The synergy between AZT in those patients and FTC was an enormous breakthrough. It led to the first combination drug, Combivir, which was the first fixed-dose combination pill. The precedent for combining drugs against drug resistance had history in cancer and even in antibiotics so there was precedent that suggested that might be the way forward. Molecular virology was progressing, understanding of DNA and RNA sequencing was progressing, so we began to find the resistant genotypes and were able to isolate the virus. That led to being able to test drugs in combination. This provided treatment for people who had exhausted their options. Now, no drug is approved for use by itself. They’re all approved for use in combination. Now if you look at antivirals, combination therapy is standard of care, it’s more potent.
Down to one pill: The next major breakthrough was the introduction of integrase inhibitors. They are nontoxic, very potent, and rapidly reduce the viral load—in two to six weeks it becomes undetectable. Now, more than 90 percent of people with HIV start treatment with just one pill once a day that includes an integrase inhibiter, and obtain an undetectable viral load.
