As therapies for HIV have advanced to help many patients control the infection as a chronic disease, investigators and patients have set their sights on a new goal: finding a cure. Leading HIV researchers Douglas Nixon and Brad Jones have recently joined Weill Cornell Medicine in the hopes of accelerating that hunt.
“We are nationally known for our HIV clinical research and our outstanding clinical care of people with HIV infections,” said Dr. Roy Gulick, chief of the Division of Infectious Diseases and principal investigator of the Cornell HIV Clinical Trials Unit at Weill Cornell Medicine. “Drs. Nixon and Jones expand that to bring an element of cutting-edge laboratory research.”
Nixon and Jones, who most recently worked at George Washington University in Washington, D.C., bring decades of combined experience studying the basic mechanisms that allow human immunodeficiency virus to avoid the immune system. They hope to collaborate with Weill Cornell Medicine clinicians and scientists to test their ideas in clinical trials.
“It’s a powerhouse for clinical trials for HIV in particular,” said Jones, assistant professor of immunology in medicine. “That was a huge draw.”
Seeking a cure
Weill Cornell Medicine’s more than 30 years of HIV/AIDS clinical trial expertise will be particularly helpful in advancing work the team is doing with the Believe in a Cure Martin Delaney Collaboratory, funded by a $28 million grant from the National Institutes of Health. The NIH awards the highly competitive grant to investigators with proven experience in innovative vaccine and immunotherapy research.
Nixon is the principal investigator of the project; he and Jones collaborate with more than a dozen other scientists from Mexico, Canada and Brazil to find and advance the most promising approaches to an HIV cure.
Existing therapies for HIV can keep the virus in check and eliminate many symptoms associated with advanced AIDS, but if patients stop taking the medications, the virus and symptoms come back. A cure would completely eliminate the virus or prevent it from causing symptoms, and may allow patients to discontinue HIV medications and avoid their side effects.
“We need a cure for HIV for a number of reasons that span from scientific to economic, but also to remove stigma from people living with HIV,” said Nixon, who was recruited to Weill Cornell Medicine as a professor of immunology in medicine in the Division of Infectious Diseases. Patients with HIV continue to face violence and discrimination in much of the world, he said, and even with successful treatment, they may experience side effects or have shortened lifespans. Additionally, the cost of antiviral drug treatments poses a financial burden in many parts of the world.
Dr. Marshall Glesby, director of the Weill Cornell HIV Clinical Trials Unit, said he hopes his team’s experience with numerous multicenter trials through the AIDS Clinical Trials Group, and their deep ties with the diverse population of people living with HIV in New York City, will help expedite the development of a much-needed cure.
“We’ve been well established in HIV clinical research, but having these elite scientists who are working on the laboratory end of things right here at Weill Cornell is really a tremendous asset,” said Glesby, professor of medicine in the Division of Infectious Diseases and professor of healthcare policy and research. Glesby and Gulick are also speakers for the International Antiviral Society-USA.“We'll really be able to expand the breadth of what we are doing at Weill Cornell.”
The work may also contribute to better treatments for patients with other diseases. Nixon said HIV research has contributed to improved care for patients with cancer and other conditions that involve the immune system.
“The study of HIV has been incredibly important in the study of human immunology because, by understanding the interaction between HIV and the immune system, we've learned more about the human immune system than we ever knew before,” Nixon said.
Cell training, ‘kick and kill’
Nixon and Jones have several lines of research underway. Investigators participating in the collaboratory are trying multiple approaches; together they decide which should advance to clinical trials. This encourages some friendly competition to have your idea tested in a clinical trial, Nixon said, and also helps the program keep up with the rapidly evolving field of HIV research.
“We are charged with constantly responding to the newest advances in the field and refocusing our research priorities accordingly,” said Jones, who was recently selected to lecture about HIV cure and vaccine research at the International AIDS Conference in Amsterdam in July 2019?.
The team is preparing to launch a preliminary clinical trial of a cell-based therapy for HIV in which a patient’s immune cells are extracted, trained to target vulnerable parts of the virus in the laboratory, then put back into the patient.That trial will begin this year in Washington, D.C., through the Children’s National Research Institute, Whitman-Walker Health – a nonprofit community health center that serves the gay, lesbian, bisexual and transgender communities and individuals with HIV – and George Washington University.
They are also working to develop more effective “kick and kill” approaches to eliminating HIV. Robert Furler, the Believe Collaboratory grant’s project manager who also has joined Weill Cornell Medicine as assistant professor of immunology in medicine, said HIV can hide in a latent state in the body, avoiding detection and destruction by the immune system and antiretroviral drugs. Many in the field have been studying ways to stir, or kick, the virus out of latency to destroy it.
“One approach in the field is to use chemicals that reverse latency while enhancing the immune system through vaccination, antibody treatment or cell therapy,” Furler said. “Researchers in Believe are testing several latency-reversing agents in combination with cell therapies or addition of broadly neutralizing antibodies to HIV.”
In addition to their ongoing projects, Jones said he’s working on two new ideas with clinical collaborators at Weill Cornell Medicine and he’s looking forward to more.
“I want to keep that pipeline going and keep expanding that,” he said, “so that there’s a constant stream of things that can be tested.”
Bridget Kuehn is a freelance writer for Weill Cornell Medicine.