Federal Project Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $515,625 Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) to The Salk Institute for Biological Studies on February 10, 2026, with a completion date of January 31, 2028. The award funds fundamental research into the molecular pathways underlying drug resistance in HIV-1 integrase, specifically examining how the virus evolves complex combinations of drug-resistant mutations (DRMs) in response to integrase strand transfer inhibitor (INSTI) therapy. The research will deliver atomic-resolution structural analyses of viral resistance mutations, computational fitness landscape models derived from extensive viral sequencing data of people living with HIV/AIDS (PLWH), and mechanistic insights into why specific mutation combinations preferentially emerge during resistance evolution.

The project's deliverables will include three key scientific outputs: (1) drug-specific mutation pathway orderings for clinically relevant triple mutant combinations using prevalence-based fitness analyses, (2) atomic-level structural determinations of how resistance mutations alter viral function and drug binding, and (3) comprehensive experimental measures of viral fitness. These research findings will advance understanding of HIV resistance mechanisms and inform optimization of antiretroviral therapy regimens, ultimately contributing to improved treatment strategies for the approximately 40 million individuals worldwide infected with HIV.