Breakthrough HIV Treatment: Gilead's Innovative Drug Discovery Journey
In 2006, Tomas Cihlar was well aware that, despite initial successes with combination therapy, HIV continued to be a global challenge with limited treatment options. At the time, he had been researching virology at Gilead for 12 years, and the first once-daily, single-tablet regimen for HIV treatment was still awaiting approval. People living with HIV had to rely on multiple daily medications, which often caused severe side effects or led to drug resistance.
“That challenge kept the Gilead research team motivated and reinforced our urgent need to develop something new,” recalls Tomas, now Senior Vice President of Research Virology.
After a decade of dedicated work, the team achieved a significant breakthrough, discovering a molecule that could transform the battle against HIV.
“In the beginning, if someone had told me where we’d eventually end up, I would have thought they were dreaming,” Tomas says with a smile. “What we discovered was completely unprecedented.”
At that time, most HIV treatments worked by targeting the viral enzymes responsible for replication and spread. However, Tomas had a different approach in mind—one that focused on the viral capsid, a cone-shaped protein structure that protects the genetic material essential for reproduction. While many scientists believed the capsid was too difficult to target, Tomas was convinced otherwise. “If we could disrupt the capsid, we might be able to stop the virus altogether,” he explains.
The research team screened hundreds of thousands of compounds, searching for one that could effectively interfere with the capsid’s function. However, their early findings were too weak to serve as viable drug candidates.
By 2009, the project faced a major roadblock, and a solution seemed out of reach. But in January 2010, Tomas attended a medical conference where a poster presentation sparked an “aha” moment, providing fresh inspiration.
“That moment revitalized our research and gave us a new direction,” he recalls.
Over the next six years, Gilead scientists synthesized and tested more than 4,000 molecules, eventually discovering a novel compound that proved exceptionally potent even at very low doses. When introduced into the human body, the molecule remained stable for several months without degrading while retaining its ability to fight the virus.
“The journey of Gilead is one of innovation, collaboration, resilience, and perseverance, and this discovery was undoubtedly a breakthrough,” Tomas reflects.
Appropriately, Breakthrough: The Quest for Life-Changing Medicines, a newly published book on medical innovation by physician-scientist and biopharmaceutical executive Dr. William Pao, explores the process of drug discovery. It highlights eight transformative medications, including Gilead’s new HIV treatment, detailing the challenges and unexpected moments that shaped their development.
“There have been many HIV treatments, but this one is truly groundbreaking,” William explains. “It represents a completely new way of thinking about the virus and targeting it. Its discovery also required a willingness to embrace unexpected opportunities—turning an insoluble molecule with a long half-life into a subcutaneous medicine.”
As Pao emphasizes in his book, drug discovery and development involve countless individuals and significant trials.
“Every drug development project has its highs and lows. Teams persist not for personal recognition, but to improve patients’ lives,” he says.
Gilead’s story is no exception.
“The unwavering commitment of hundreds of people—from Gilead’s research and development teams to external collaborators and clinical trial participants—made this achievement possible,” Tomas states. “This story demonstrates what can be accomplished when we set ambitious goals and work together to achieve them.”
Recent clinical trial results suggest that this drug could potentially prevent HIV transmission entirely. If regulatory approval is granted, Gilead has already developed a global access strategy to ensure its availability in low- and middle-income countries.
“That challenge kept the Gilead research team motivated and reinforced our urgent need to develop something new,” recalls Tomas, now Senior Vice President of Research Virology.
After a decade of dedicated work, the team achieved a significant breakthrough, discovering a molecule that could transform the battle against HIV.
“In the beginning, if someone had told me where we’d eventually end up, I would have thought they were dreaming,” Tomas says with a smile. “What we discovered was completely unprecedented.”
At that time, most HIV treatments worked by targeting the viral enzymes responsible for replication and spread. However, Tomas had a different approach in mind—one that focused on the viral capsid, a cone-shaped protein structure that protects the genetic material essential for reproduction. While many scientists believed the capsid was too difficult to target, Tomas was convinced otherwise. “If we could disrupt the capsid, we might be able to stop the virus altogether,” he explains.
The research team screened hundreds of thousands of compounds, searching for one that could effectively interfere with the capsid’s function. However, their early findings were too weak to serve as viable drug candidates.
By 2009, the project faced a major roadblock, and a solution seemed out of reach. But in January 2010, Tomas attended a medical conference where a poster presentation sparked an “aha” moment, providing fresh inspiration.
“That moment revitalized our research and gave us a new direction,” he recalls.
Over the next six years, Gilead scientists synthesized and tested more than 4,000 molecules, eventually discovering a novel compound that proved exceptionally potent even at very low doses. When introduced into the human body, the molecule remained stable for several months without degrading while retaining its ability to fight the virus.
“The journey of Gilead is one of innovation, collaboration, resilience, and perseverance, and this discovery was undoubtedly a breakthrough,” Tomas reflects.
Appropriately, Breakthrough: The Quest for Life-Changing Medicines, a newly published book on medical innovation by physician-scientist and biopharmaceutical executive Dr. William Pao, explores the process of drug discovery. It highlights eight transformative medications, including Gilead’s new HIV treatment, detailing the challenges and unexpected moments that shaped their development.
“There have been many HIV treatments, but this one is truly groundbreaking,” William explains. “It represents a completely new way of thinking about the virus and targeting it. Its discovery also required a willingness to embrace unexpected opportunities—turning an insoluble molecule with a long half-life into a subcutaneous medicine.”
As Pao emphasizes in his book, drug discovery and development involve countless individuals and significant trials.
“Every drug development project has its highs and lows. Teams persist not for personal recognition, but to improve patients’ lives,” he says.
Gilead’s story is no exception.
“The unwavering commitment of hundreds of people—from Gilead’s research and development teams to external collaborators and clinical trial participants—made this achievement possible,” Tomas states. “This story demonstrates what can be accomplished when we set ambitious goals and work together to achieve them.”
Recent clinical trial results suggest that this drug could potentially prevent HIV transmission entirely. If regulatory approval is granted, Gilead has already developed a global access strategy to ensure its availability in low- and middle-income countries.
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