Project Grant R21AI198010

The National Institute of Allergy and Infectious Diseases awarded the University of Tennessee Health Science Center $231,000 on August 14, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate HIV integrase strand transfer inhibitors as potential antifungal agents against Cryptococcus species.

The research examines whether multiple integrase inhibitors—including bictegravir, dolutegravir, raltegravir, elvitegravir, and cabotegravir—inhibit cryptococcal growth in vitro and in vivo. Prior work identified anti-cryptococcal activity across multiple Cryptococcus strains and demonstrated additive or synergistic effects when combined with existing antifungal drugs such as amphotericin B, flucytosine, and fluconazole. A murine infection model showed elvitegravir treatment reduced fungal burden, with further enhancement when combined with fluconazole. The award funds continued investigation of the fungal protein targets underlying these effects using computational structural approaches to identify Cryptococcus proteins with tertiary structure similarity to HIV-1 integrase.

The work addresses a critical gap in antifungal treatment. Cryptococcus neoformans causes approximately 250,000 cases of cryptococcal meningitis annually and over 180,000 deaths worldwide, with annual economic burden in the United States exceeding $535 million. Current antifungals face limitations including toxicity, limited drug classes, emerging resistance, and medication shortages.

Performance occurs in Memphis, Tennessee, with a period of performance from the award date through July 31, 2028.