Project Grant R01AI194900

The National Institute of Allergy and Infectious Diseases awarded the Regents of the University of Minnesota $1,139,609 on August 10, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct a randomized trial evaluating the optimal timing of antiretroviral therapy initiation in persons with early disseminated cryptococcal infection.

The project will address gaps in international clinical guidance by rigorously evaluating the safest and most effective timing for antiretroviral therapy initiation to maximize survival among asymptomatic cryptococcal antigenemia-positive persons with advanced HIV disease, and determining the optimal duration of preemptive fluconazole therapy for asymptomatic cases with low titers. Cryptococcus remains the leading cause of HIV-related meningitis, and cryptococcal antigenemia is detectable weeks before meningitis onset, offering a critical window for intervention. Current conflicting guidelines have resulted in potentially harmful delays for patients with advanced HIV disease. Ten weeks of preemptive fluconazole therapy has demonstrated a 28 percent survival benefit in trials, yet World Health Organization guidelines recommend an extended six-month treatment course based on expert opinion alone, driving unnecessary costs, excessive antifungal exposure, and missed opportunities for streamlined care.

Performance occurs at the University of Minnesota in Minneapolis, Minnesota. The period of performance runs from August 10, 2026, through July 31, 2031. The award is a Project Grant, a form of assistance funding supporting biomedical research in infectious diseases and related areas.