Facing Down Pandemics: Dr. Larry Corey on HIV and COVID-19

By: Sabin Russell, Fred Hutch News Service, Seattle, WA, USA

Dr. Larry Corey

Dr. Larry Corey, Principal Investigator, HVTN, Seattle, WA, USA

Credit: Matt Hagen

When Dr. Larry Corey first heard reports of a respiratory virus spreading rapidly in Wuhan, China, the renowned virologist and former President and Director of Fred Hutchinson Cancer Research Center felt that unsettling sense of déjà vu.

“As you saw the devastation that it was causing in Wuhan, and you understood the transportation patterns and the people flow in China, you started to understand the implications,” said Corey, during a recent interview for HVTN Community Compass.

“In many respects, COVID-19’s a re-living of what happened 39 years ago in HIV, when it was difficult and frustrating,” he said. “The lesson that we learned then is that when the academic, biotech and pharmaceutical communities put their collective scientific assets together, things happen.”

In June 1981, as a University of Washington researcher then working on a treatment for genital herpes, Corey read in the Centers for Disease Control’s weekly newsletter a brief report of five cases of gay men in Los Angeles felled by Pneumocystis carinii, a rare pneumonia previously found in people with compromised immune systems.

It would be another two years before the Pasteur Institute’s Drs. Francoise Barre-Sinoussi and Luc Montagnier isolated the retrovirus later proven to be the cause of it, and still years before the global impact of HIV would be fully comprehended.

Yet that tiny virus quickly transformed the trajectory of Corey’s career. The deep ties he had developed with the community as a researcher in sexually transmitted diseases propelled him into a leadership role in fighting stigma, bigotry and fear. As the world struggled to understand HIV, he rose to become an authoritative voice on how to treat it with antiviral drugs.

As chairman of the AIDS Clinical Trials Group, he shuttled from Seattle to Washington D.C. to oversee critical trials, first proving that AZT could protect newborns of HIV-positive mothers, then launching the trials on combination therapies that have since saved millions of lives. Then his focused shifted to vaccines.

In 1998, at the urging of National Institute of Allergy and Infectious Diseases director Dr. Tony Fauci, Corey co-founded the HIV Vaccine Trials Network, headquartered at Fred Hutch. One of the first people he hired was Steve Wakefield, who today leads HVTN’s global efforts for stakeholder engagement.

“Larry has a deep moral conviction to take care of the world that he’s in with the talents that he has,” Wakefield told Fred Hutch writer Mary Engel. “But he didn’t get any recognition for the sacrifices he’s made to solve this epidemic. Until he had his grandchildren, I never remember him going on vacations. Now, part of his drive to find a vaccine is so his grandchildren will never have to live with HIV.”

Over decades, the tireless quest for an HIV/AIDS vaccine has weathered a string of disappointments. The vaccines tested in carefully designed clinical trials have so far failed, but as the body of knowledge about the immune system continues to expand, Corey remains cautiously, but steadfastly, optimistic.

In early February, he had to deliver the news that the Uhambo trial, HVTN 702, showed no efficacy and was shutting down. The hope had been that this vaccine regimen would improve upon an earlier version found modestly effective in a large trial in Thailand in 2009. Instead, it showed no effectiveness at all.

“You did a damn good job,” he told a gathering of staffers at Fred Hutch. “It was a painful answer, but our job is to do these studies, and you did it incredibly well.”

Later that month, Corey met with his South African counterparts and the disappointed participants in Cape Town to thank them for their courage and to assure them that the quest will go on.

“One trial of five failed, but we still have four more out in the field,” he said in his recent interview. “There is sadness, but science is about resilience. You have to have optimism, resilience and perseverance.”

By year-end, Corey anticipates results from the recently completed Antibody Mediated Prevention, or AMP, studies, where over 40,000 infusions of broadly neutralizing antibodies were given to volunteers. One other HVTN trial, Imbokodo, is fully enrolled with ongoing follow-up underway, and a related trial, Mosaico, was just getting underway when COVID-19 struck.

“Altruism and concern about HIV are alive and well, and you certainly see it in the MSM and transgender communities in the U.S. and South America, and among the people of southern Africa,” he said.

Yet the impact of COVID-19 was coming quickly, even to South Africa. Corey had to cut his trip short and return to Seattle, where he is coordinating multiple efforts with Fred Hutch, the University of Washington (UW), the Bill & Melinda Gates Foundation, and other community partners to respond to the latest threat.

Cruelly underscoring the interconnectedness of the struggle against pandemic viruses, the HVTN community learned in March that Dr. Gita Ramjee died of COVID-19 in March, soon after returning to Durban, South Africa, from a visit with her sons in London. She was 63.

“It is so sad when you see so many deaths happening. When a colleague passes away prematurely, it’s a loss in our family, but also for the world,” Corey said.

With a new pandemic underway, he once again stands in the forefront of scientific efforts to stop a global threat. When COVID-19 reached Seattle, its first significant toehold in North America, researchers at Fred Hutch, UW and Public Health-King County & Seattle, responded decisively because of the deep understanding of virology and the infrastructure of laboratories and expertise that Corey had built over four decades of confronting HIV.

“I came to this city that I love 42 years ago as a UW faculty member to start a virology division. I inherited a program in a small lab in the basement of Children’s Hospital,” he recalled. “And we built it into the largest academically based virology lab in the country. Then of course we set up the Vaccine and Infectious Disease Division at Fred Hutch, and between UW and the Hutch, I believe it’s the largest faculty in infectious diseases in the country.”

“We trained an enormous number of people in viral disease. So, it is gratifying to see how that infrastructure presented Seattle with the opportunity to handle this new epidemic. It allowed us to do COVID-19 testing at a rate better than essentially any other city, and that has been an incredible factor in our response.”

Sabin Russell is a writer and editor for the Fred Hutch News.