In 2006, Tomas Cihlar knew all too well that despite initial successes with combination treatment, HIV was firmly holding ground around the globe and existing therapies were limited. He was 12 years into his virology research career at Gilead and the first daily single tablet regimen for HIV treatment was still awaiting approval. Treatment options for people living with HIV at the time were a raft of daily medications that often carried intolerable side-effects, or the virus became resistant to the medications.

“That’s what kept the research team at Gilead awake and stirred our urgent imperative to create something different,” recalls Tomas, now Senior Vice President, Research Virology.

Ten arduous years later, the researchers made significant progress toward their goal by creating a molecule that has the potential to help revolutionize the fight against HIV.

“In the beginning, if somebody told me that we’d end up where we are now, I would say, ‘You’re a dreamer,’” Tomas says, smiling. “What we ended up discovering was completely novel.”

At the time, most existing HIV drugs worked by interfering with the viral enzymes that HIV uses to multiply and spread throughout the body. But Tomas envisioned a different solution – one that disrupted the viral capsid, the cone-shaped protein structure that holds the genes essential for viral reproduction. Most scientists thought the capsid was too difficult to target, but the Czech-born biochemist was convinced otherwise. “The capsid protects the genetic material of the virus. If you can interfere with that, you could potentially stop the virus,” he explains.

So the team began screening hundreds of thousands of compounds, looking for one that could disrupt the capsid's function. But the ones they initially found were too weak to be effective as future drugs.

By 2009, the researchers almost reached a dead end when they couldn’t seem to find a solution. But then a poster at a medical conference in January 2010 caught Tomas’ eye and provided an ‘aha moment’ and some new inspiration.

“That breathed new life into the research project and gave us new direction,” he says.

In the six years that followed, Gilead scientists synthesized and tested over 4,000 molecules which led to the discovery of a novel molecule that proved to be remarkably potent at extremely low concentrations. The new molecule, when injected into the human body, was found to be very stable and retained its viral-fighting properties for several months without degrading.

“The Gilead story is a classic tale of innovation, collaboration, resilience and determination and this was definitely a breakthrough point,” Tomas acknowledges.

Fittingly, Breakthrough, The Quest for Life-Changing Medicines is the name of a newly released book about innovation in drug discovery that examines eight medications that have had a significant impact on patients around the world. Written by physician-scientist and biopharmaceutical executive Dr. William Pao, the book devotes a chapter to Gilead’s new HIV medicine, while detailing the improbable journey and numerous obstacles that stood in the way of Gilead scientists.

“There have been a number of medicines for HIV, but this is really transformative,” William says. “It’s a completely different way of thinking about the virus and attacking it. Its discovery also required embracing the serendipity that is making an insoluble molecule with a long half-life into a subcutaneous medicine.” 

As Pao notes throughout his book, the process of drug discovery and development involves many people and many trials.

“Every project in drug development has its ups and downs. Teams persist with resilience and determination not for their own glory, but for the benefits of patients,” he says.

And this Gilead story is no exception.

“The sheer determination of hundreds of people not only in Gilead research and development, but also external partners and all the participants in clinical trials, contributed to the outcome,” says Tomas. “This is a story that really shows people how things can turn out when we set our mind to an ambitious goal and work together to achieve it.”

Results of recent clinical trials show that the drug has the potential to prevent HIV transmission altogether. The company has devised a global access strategy for its supply in low- and middle-income countries if it obtains regulatory approval.