Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Enhanced Antifungal Therapy to Improve Survival in Early Disseminated Cryptococcal Infection

Award Number: U01AI174978
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/21/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

Group Awards By:

View Award Description

Enhanced Antifungal Therapy to Improve Survival in Early Disseminated Cryptococcal Infection - Abstract Cryptococcal meningitis is the most common adult neuroinfection in sub-Saharan Africa and causes ~15% of AIDS-related mortality globally. In the weeks prior to onset of meningitis, cryptococcal antigen (CrAg) is detectable in the blood, and is a predictor of meningitis and death. CrAg screening in plasma is an effective public health strategy to identify persons with CD4<200 cells/mcL at high risk of meningitis and death. In a randomized trial of 2000 persons with HIV, CrAg screening and preemptive fluconazole treatment yielded a 28% survival benefit over standard-of-care. As a result, the World Health Organization and U.S. guidelines recommend CrAg screening. Yet despite the survival benefit seen with CrAg screening and preemptive therapy, 25% of initially asymptomatic CrAg+ persons treated with fluconazole still die, even with HIV therapy. From 4 prospective cohort studies of CrAg+ persons in Africa, we have determined that as plasma CrAg titer increases, mortality increases, despite fluconazole therapy. Among asymptomatic CrAg+ persons, disseminated cryptococcosis is the most commonly identified cause of death. We posit that subclinical disseminated early neuroinfection in the brain parenchyma accompanies high CrAg titers, and fluconazole is inadequate therapy. More effective treatment is critically needed to reduce mortality in CrAg+ persons. For symptomatic cryptococcal meningitis, amphotericin B is the most effective antifungal; fluconazole alone is inadequate. Recent randomized trial data reported single dose of liposomal amphotericin (AmBisome) 10 mg /kg with flucytosine (5FC) and fluconazole is as effective and less toxic than the traditional 7-day amphotericin + 5FC for meningitis. We hypothesize that AmBisome (10mg/kg x1), when combined with fluconazole, will be more effective than fluconazole monotherapy for asymptomatic CrAg+ persons. We have enrolled 244 CrAg+ persons in the initial phase II of a phase II/III randomized trial to demonstrate safety and feasibility of this enhanced regimen in Uganda, and now we seek to complete the phase III trial in order to test efficacy. The objective of this application is to assess the efficacy of AmBisome plus fluconazole to prevent cryptococcal meningitis and death. We will complete a randomized clinical trial of 600 CrAg+ persons (i.e. 356 more participants) to determine if preemptive therapy with AmBisome (10mg/kg x1) plus fluconazole for CrAg+ persons will improve cryptococcal meningitis-free 6-month survival compared with the current standard of fluconazole monotherapy (Aim 1). In Aim 2, we will determine if neurocognitive outcomes in CrAg+ persons preemptively treated with AmBisome with fluconazole are superior to outcomes with fluconazole monotherapy. Finally, in Aim 3 we will evaluate the cost and cost-effectiveness of AmBisome with fluconazole preemptive treatment in CrAg+ persons. Findings from this trial will impact U.S. and international HIV guidelines on the optimal prevention of cryptococcal meningitis, in order to reduce mortality in persons living with HIV.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $623,681 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	4	4/7/2026	NON-COMPETING CONTINUATION	$364,500
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Allergy and Infectious Diseases Research	001	4	4/17/2026	SUPPLEMENT FOR EXPANSION	$259,181
														Subtotal = $623,681

Issue Date FY: 2025 ( Subtotal = $631,690 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	3	8/14/2025	NON-COMPETING CONTINUATION	$356,777
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Allergy and Infectious Diseases Research	001	3	8/15/2025	SUPPLEMENT FOR EXPANSION	$274,913
														Subtotal = $631,690

Issue Date FY: 2024 ( Subtotal = $638,152 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	2	3/28/2024	NON-COMPETING CONTINUATION	$638,152
														Subtotal = $638,152

Issue Date FY: 2023 ( Subtotal = $676,872 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	1	4/21/2023	NEW	$676,872
														Subtotal = $676,872

Grand Total All Awards = $2,570,395

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Enhanced Antifungal Therapy to Improve Survival in Early Disseminated Cryptococcal Infection

Award Number: U01AI174978

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/21/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer