Federal Grant Award Summary

The University of Pittsburgh received a $790,847 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded February 10, 2026, with completion targeted for January 31, 2031. This award supports comprehensive research investigating HIV-1 resistance pathways against lenacapavir (LEN), a potent capsid inhibitor under investigation for both treatment and prevention applications. The research will deliver scientific products including characterization of HIV-1 drug resistance mechanisms, mapping of resistance-conferring mutations through large-scale mutant libraries and multiplex selection approaches, and determination of how capsid (CA) mutations affect viral fitness and transmissibility.

The funded research will produce both in vitro and in vivo experimental data examining lenacapavir-resistant HIV-1 variants using accelerated evolution approaches and humanized mouse models. Key deliverables include identification of novel resistance mutations and their evolutionary trajectories, assessment of viral fitness in lenacapavir-treated humanized mice, evaluation of transmission efficiency of resistant variants in mucosal transmission models, and identification of phenotypic correlates associated with transmissibility of resistant variants. These research outcomes will inform clinical understanding of capsid inhibitor resistance and its implications for future HIV prevention and treatment strategies.