Clinical trial NCT04033120: Making an Early Diagnosis of Talaromycosis Using a Novel Antigen Test
Official title: Making an Early Diagnosis of Talaromycosis - a Strategy to Reduce Morbidity and Mortality in Advanced HIV Disease in Southeast Asia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: AIDS/HIV - RelatedDisease Associated With AIDS
Keywords: HIV
talaromycosis
endemic mycoses
opportunistic infections
penicilliosis
Southeast Asia
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Oxford University Clinical Research Unit, Vietnam
name: National Hospital for Tropical Diseases, Hanoi, Vietnam
name: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
name: The University of Hong Kong
First posted: 2019-07-25
Enrollment: 1411
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-infected patients age ≥18 years with advanced HIV disease who have a CD4 count ≤100 cells/mm3 within the past 3 months, who are admitted to hospitals with a suspected infection (Cohort 1) or who are asymptomatic and registered in HIV outpatient clinic (Cohort 2) in Vietnam

Brief summary: This is a research study to determine whether a new antigen detection test called Mp1p EIA can make an early diagnosis of talaromycosis from the blood and urine of patients. Talaromycosis is a life-threatening infection caused by a fungus endemic in Southeast Asia commonly found in patients with advanced HIV disease called Talaromyces marneffei.

Detailed description: This study aims to determine the diagnostic and prognostic values and the clinical impact of Talaromyces marneffei antigenemia (TmAg) in patients with advanced HIV disease using a novel enzyme immunoassay (EIA) detecting Tm-specific cell wall mannoprotein Mp1p. The data generated will be used to inform the design of future diagnostic clinical trials to test the utility of screening and providing pre-emptive antifungal therapy to prevent disease and reduce HIV mortality in Southeast Asia.

The primary objective is to screen for TmAg and determine its diagnostic and prognostic performance in symptomatic and asymptomatic HIV-infected patients with a CD4 count ≤100 cells/mm3.

We will test the following hypotheses:

1. In symptomatic hospitalized patient Cohort 1, the sensitivity of the Mp1p EIA will be higher than conventional culture method while simultaneously specificity is higher than 95% for diagnosing culture-confirmed talaromycosis over a six-month follow up period
2. In asymptomatic outpatient Cohort 2, there will be at least 30% difference in risk of talaromycosis development in TmAg-positive patients compared to TmAg-negative patients over a twelve-month follow up period
3. TmAg concentration predicts development of talaromycosis

Secondary Objectives include:

1. To assess the impact of presence of TmAg on clinical outcomes, including development of culture-confirmed talaromycosis, incidence of state III and IV AIDS events, subsequent hospitalizations, and death over six- to twelve-month follow up periods
2. To compare the diagnostic values of the Mp1p EIA when performed in plasma, sera, and urine samples and when performed in these matrices in combination

   We will test the following hypotheses:
3. To model the health economic benefits of screening and pre-emptive treatment for pre-clinical infection
4. To assess impact on clinic outcomes of screening all patients for cryptococcosis and histoplasmosis
5. To collect additional blood samples and store left-over samples for future research to validate infectious disease diagnostics and research to understand genetic susceptibility to infectious diseases relevant to HIV population

Participants in the study, will be asked questions about their medical and travel history. Participants will have blood and urine collected for the Mp1p EIA test to look for early talaromycosis infection and for other tests to look for common HIV-associated infections including tuberculosis, cryptococcosis, and histoplasmosis. They will be examined by a study doctor at least once weekly if they are in the hospital and will be followed in clinic monthly for between 6 and 12 months.

Eligibility criteria: Inclusion Criteria:

1. HIV-1 infection (at least 2 of 3 HIV antibody tests are positive), AND
2. HIV-infected age ≥18 years, AND
3. CD4 count ≤100 cells/mm3 within the past 3 months, AND
4. Antiretroviral therapy (ART) naïve OR recent ART ≤3 months OR suspected or confirmed treatment failure on ART ≥12 months (defined as poor treatment adherence, treatment interruption, or having a confirmed HIV RNA ≥1,000 copies)
5. Cohort 1: suspected to have an active infection
6. Cohort 2: not suspected to have or being evaluated for an active infection

Exclusion Criteria:

1. Unlikely to attend regular clinic visits
2. History of recent talaromycosis or histoplasmosis infection currently on antifungal therapy

Primary outcomes:
measure: Incidence of microscopy and/or culture-confirmed talaromycosis
timeFrame: over six to twelve months
Secondary outcomes:
measure: Incidence of other major HIV-associated opportunistic infections
timeFrame: over six to twelve months
measure: Incidence of stage III and IV AIDS events
timeFrame: over six to twelve months
measure: Hospitalizations in the subsequent six to twelve months
timeFrame: over six to twelve months
measure: Mortality in the subsequent six months (Cohort 1) and twelve months (Cohort 2)
timeFrame: over six to twelve months
measure: Incidence of loss to follow up
timeFrame: over six to twelve months
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: Hospital for Tropical Diseases
state: Ward 1 District 5
city: Hà Nội
country: Vietnam
facility: National Hospital for Tropical Diseases
Study officials:
affiliation: Duke University
name: Thuy Le, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thu NTM, Chan JFW, Ly VT, Ngo HT, Hien HTA, Lan NPH, Chau NVV, Cai JP, Woo PCY, Day JN, van Doorn R, Thwaites G, Perfect J, Yuen K, Le T. Superiority of a Novel Mp1p Antigen Detection Enzyme Immunoassay Compared to Standard BACTEC Blood Culture in the Diagnosis of Talaromycosis. Clin Infect Dis. 2021 Jul 15;73(2):e330-e336. doi: 10.1093/cid/ciaa826.