Fogarty Fellow: Tessa Adzemovic

Tessa Adzemovic

Nominated From: University of Michigan 
Research Site: Infectious Disease Institute, Makerere University 
Primary Mentor: David Boulware

Research Project

Neurocognitive Outcomes on Encochleated Oral Amphotericin for HIV-associated Cryptococcal Meningitis: sub-study of the EnACT3 Phase III Trial

While it is true that there is an asymmetric burden of Cryptococcus meningitis in resource-limited areas, Cryptococcus remains a concern for individuals living with HIV/AIDS in the United States. 1 IDSA guidelines have not changed over the last ten years when it comes to treatment of Cryptococcus, and the EnACT3 trial could have practice-changing implications in both Sub-Saharan Africa, as well as the United States. This sub-study, which will define neurocognitive outcomes, will play an instrumental role in this, given the duration and severity of neurocognitive deficits after Cryptococcal infection.

Cryptococcal meningitis has become the most common cause of adult meningitis in many parts of Africa where cryptococcosis now rivals tuberculosis in all-cause mortality. As such, the identification of additional antifungals effective for the treatment of cryptococcal meningitis is a public health priority. Historically amphotericin B (AMB) has been the treatment of choice for patients with Cryptococcal meningitis, given its broad spectrum of activity. The Encochleated Oral Amphotericin for Cryptococcal Meningitis (ENACT3) trial is a prospective, randomized, open-label, non-inferiority study to compare the efficacy and safety of step-down induction and consolidation therapy for the treatment of cryptococcal meningitis with oral amphotericin B + 5FC to standard of care, with all-cause mortality as the primary endpoint. It is known that neurocognitive outcomes are the largest source of morbidity for patients with cryptococcal meningitis. Thus, understanding how oral amphotericin may affect neurocognitive outcomes is a crucial component to appraising the efficacy of this medication. As such, I propose a sub-study to evaluate neurocognitive outcomes in subjects being treated for cryptococcal meningitis with the hope that the outcomes of the study will help to predict whether individuals living with the disease will be able to return to healthy, active, and independent lifestyles.