Joshua Rhein, MD
Nominated From: University of Minnesota
Research Site: Uganda
Research Area: Infectious Disease
Primary Mentor: David Boulware
Adjunctive Sertraline for the Treatment of HIV-associated Cryptococcal Meningitis
Dr. Rhein is a translational researcher combining his infectious disease training with basic science investigations into disease pathogenesis. His primary research interests are CNS infections in resource-limited areas, specifically cryptococcal meningitis, as well as HIV immune reconstitution inflammatory syndrome (IRIS). Dr. Rhein’s current research is focused on improving the clinical outcomes of HIV-infected persons with cryptococcal meningitis.
Recent evidence suggests that the commonly used selective serotonin reuptake inhibitor (SSRI) sertraline provides potent in vitro fungicidal activity against Cryptococcus neoformans and readily crosses the blood-brain barrier being concentrated an average of 22-fold higher in brain tissue. In murine models, sertraline’s microbiologic activity equaled that of fluconazole and was synergistic with fluconazole. Taken together, sertraline offers a promising possible therapeutic oral option for CM treatment. We hypothesize that sertraline added to standard amphotericin and fluconazole CM induction therapy will result in improved survival.
Cryptococcal meningitis (CM) has emerged as one of the most frequent and deadly opportunistic infections in HIV patients, causing 20% of AIDS-related mortality. Early mortality from HIV-associated CM remains unacceptably high, in large part due to the high cost, toxicity, and relatively limited repertoire of effective antifungals. Furthermore, the rate of fungal clearance from cerebrospinal fluid (CSF) for currently available CM treatment regimens remains low, meaning that sterilization after 2 weeks of induction therapy cannot always be ensured. For these reasons, the identification of new effective antifungals is of utmost importance.
Advice for Applicants:
Mentorship is of primary importance whether you are just beginning a career in global health research or are already an established researcher. Site-specific collaborators are equally important to a successful research project, as is an open mind and an abundance of flexibility.