Weill Cornell Medicine is spearheading a $14.9 million, five-year initiative to develop personalized cures for HIV, backed by a grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
The multi-institutional effort seeks to eliminate latent HIV from infected cells, transforming HIV management from lifelong treatment to potential cure.
Globally, over 40 million people live with HIV, according to the World Health Organization. Current antiretroviral therapies (ART) can suppress the virus to near-undetectable levels, but HIV can persist in a latent form within certain cells.
If ART is discontinued, these latent reservoirs can reactivate, making the virus transmissible and eventually leading to AIDS. Researchers now view the latent viral reservoir as the central obstacle to achieving an HIV cure.
The research program, titled Innovative Strategies for Personalized Immunotherapies and Reservoir Eradication (INSPIRE), will be led by Dr. Brad Jones, associate professor of microbiology and immunology in Weill Cornell Medicine’s Division of Infectious Diseases.
“This award validates our ongoing work and confirms that Weill Cornell Medicine has become a major global hub for HIV cure research,” Dr. Jones said.
HIV integrates its DNA into the genomes of infected cells, primarily targeting CD4+ T cells. In some cases, the viral DNA remains dormant, making these reservoir cells difficult to detect. The reservoir’s composition and activity vary between individuals and over time, complicating treatment efforts.
INSPIRE aims to map these HIV-harboring cells to understand their vulnerabilities to immune system attacks. Researchers will study a collection of reservoir cells previously isolated from people with HIV to identify different types of reservoirs and potential therapeutic targets.
Guided by these insights, the team plans to explore innovative treatment strategies inspired by cancer immunotherapy. These approaches include engineering patients’ own T cells or natural killer (NK) cells to selectively attack reservoir cells.
“Because the reservoir and immune responses vary among individuals, effective cures will likely require personalized approaches, similar to cancer therapies,” said co-principal investigator Dr. Marina Caskey of Rockefeller University. “Our goal is to develop tailored immunotherapies using broadly neutralizing antibodies to achieve durable, ART-free HIV remission.”
The team will also investigate engineering patients’ B cells to produce a long-lasting supply of broadly neutralizing antibodies against HIV, providing continuous immune defense much like a vaccine. These antibodies can target diverse HIV strains and could suppress the reservoir, potentially reducing viral persistence over time.
“Broadly neutralizing antibodies in the bloodstream long-term should suppress HIV reservoirs and prevent viral rebound without ongoing ART,” Dr. Jones explained. “This strategy may even shrink the reservoir gradually, bringing us closer to a functional cure.”
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