# Improving Outcomes of HIV-Associated Cryptococcosis in Resource-Limited Settings

> **NIH NIH K01** · UNIVERSITY OF MINNESOTA · 2020 · $140,697

## Abstract

Cryptococcal meningitis (CM) remains a major cause of HIV-related mortality in Africa. Successful
management of Cryptococcus in resource-limited areas is often hindered by unsatisfactory or unavailable
antifungal regimens. In these settings, treatment failure and relapse are common. Furthermore, widespread
availability of ART has led to changes in the meningitis epidemiology in Africa. Persons with cryptococcal
meningitis now have more complex disease presentations, with 40-50% presenting while receiving ART. Large
knowledge gaps exist in the diagnosis and management of increasing proportions of complex patients, in
particular those developing cryptococcal meningitis shortly after initiating ART, second episodes due to
paradoxical immune reconstitution inflammatory syndrome (IRIS) with sterile CSF, or second episodes of
culture-positive relapse.
 This mentored international research project is a prospective cohort study of HIV-infected Africans with
Cryptococcus in Uganda. The candidate will determine if persons who develop cryptococcal meningitis while
already receiving ART will have worse outcomes compared to ART-naïve persons in a resource-limited area.
The candidate will evaluate whether differential outcomes based on ART status are dependent on expression
of biomarkers in cerebrospinal fluid (CSF). Specifically, the candidate will assess whether persons receiving
effective ART will have inflammatory patterns of biomarker expression in CSF. Finally, in cases of recurrent
symptomatic meningitis, the candidate will evaluate the role of novel laboratory techniques and biomarkers as
more sensitive indicators of infection for rapid differentiation of paradoxical IRIS from culture-positive relapse.
 Dr. Rhein's long-term career goal is to become an independent translational global health researcher
who bridges the gap between basic science and clinical research, moving basic science concepts to clinical
application in resource-limited settings. During his training to date, Dr. Rhein has spent 4 years on the ground
in Kampala, Uganda working on cryptococcal meningitis research. This K01 award will provide for mentored
career development using a combination of coursework to supplement current knowledge gaps and practical
mentored-research experience to build a strong foundation of laboratory research skills in HIV immunology and
CNS pathogenesis. The award will build upon existing international collaborations and help the candidate
develop experience in clinical trial design and implementation in an international setting.

## Key facts

- **NIH application ID:** 9893041
- **Project number:** 5K01TW010268-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Joshua R Rhein
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $140,697
- **Award type:** 5
- **Project period:** 2016-09-28 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893041

## Citation

> US National Institutes of Health, RePORTER application 9893041, Improving Outcomes of HIV-Associated Cryptococcosis in Resource-Limited Settings (5K01TW010268-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9893041. Licensed CC0.

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