HIV remains in the body during antiretroviral therapy (ART), and the virus usually returns if treatment is stopped. One of its most durable hiding places is in long-lived memory CD4+ T cells, especially in tissues such as the gut and lymph nodes. We hypothesize that the same cellular programs that preserve these tissue immune cells in a long-lived, resting state also help keep HIV silent during ART.
Within tissues, these resting-cell programs are supported by immunometabolic adaptations that limit T-cell activation and proliferation, protecting against excessive responses to persistent infection and inflammation. They may act as “white noise,” raising the threshold for both immune-cell activation and HIV reawakening. We are investigating this idea by targeting TGF-β, a key regulator of mucosal immunity, tissue repair, and immune metabolism. TGF-β remains elevated despite long-term HIV treatment and may contribute to chronic inflammation, premature aging, and HIV-associated comorbidities.
​
We test whether temporarily blocking TGF-β can expose latent HIV in tissues and make infected cells more vulnerable to immune- and virus-mediated elimination. Using clinically advanced TGF-β inhibitors in rhesus macaque models, immunoPET/CT imaging with a labeled HIV/SIV probe, and single-cell and spatial transcriptomics, we track where virus becomes active and define how tissue immunometabolic programs sustain the viral reservoir. Our goal is to advance a functional cure for HIV by developing interventions that enable durable virologic control without ongoing antiretroviral therapy.
