Point of Care Tests to Identify Opportunistic Infections in Advanced HIV Patients in Mexico City

Study Overview
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Brief Summary
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In Mexico City, the main cause of mortality among people living with HIV (PLHIV) continues to be opportunistic infections (OIs). Early detection of OIs allows their timely treatment and improves their prognosis. The use of rapid diagnostic tests (RDT) based on antigens of the most frequent causative agents of OIs allows adequate screening of these patients and facilitates decision making at the point of care. Unfortunately, these studies are not widely available in the different PLHIV care centers in the CDMX. We will conduct an open-label, non-inferiority uncontrolled clinical trial to investigate the diagnostic performance of urinary lipoarabinomannan, urinary Histoplasma antigen and serum Cryptococcus antigen in patients presenting for care with advanced HIV in CDMX, supported by rapid cluster of differentiation 4 (CD4) testing with lateral flow technology. Four referral hospitals will participate over 12 months. All patients with diagnosed HIV disease and suspected advanced disease presenting for care at participating centers will be included in the study. An inventory of approximately 1000 RDT will be obtained and distributed among the participating sites. A study coordinator will be hired and will visit each site once a week to collect the study variables and follow up on the included patients. The primary outcome of the study will be the percentage of patients with advanced disease who present with diagnoses made by RDT compared to historical controls of patients diagnosed with OI in 2022 at participating centers by conventional methods. Secondary outcomes will be time to initiation of antiretroviral therapy (ART), time to initiation of OI treatment, and 30-day mortality after HIV diagnosis.

Official Title
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Implementation Protocol for Rapid Diagnostic Tests for Opportunistic Infections in Reference Centers in Mexico City

Conditions
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Acquired Immunodeficiency Syndrome, Histoplasmosis AIDS, Tuberculosis Infection, Cryptococcal Meningitis

Intervention / Treatment
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* Diagnostic Test: Histoplasma Urine Antigen Lateral Flow Antigen test
* Diagnostic Test: Cryptococcal Lateral Flow Antigen test
* Diagnostic Test: Tuberculosis-lipoarabinomannan Lateral Flow Antigen test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive ELISA test or positive viral load for HIV. Patients with suspected or confirmed advanced HIV disease defined as follows: Confirmed: asymptomatic patients with CD4 count less than 200 cells/ml within 3 months of study inclusion or confirmed diagnosis of an AIDS-defining opportunistic illness within the last 3 months. Suspected: patients who, irrespective of CD4 count, present any symptoms suggestive of systemic infection that, at the discretion of the treating physicians, produce suspicion of an AIDS-defining opportunistic disease (e.g., fever, productive cough, diaphragmatic diapers, etc.). Fever, productive cough, nocturnal diaphoresis, altered mental status, headache, lymphadenopathy, dermatological lesions) or that meet criteria for HIV wasting syndrome (loss of 10% of baseline weight plus the presence of chronic diarrhea or chronic weakness and an episode of fever in the last 30 days). Patients without effective antiretroviral therapy defined as not having received antiretroviral treatment in the last 3 months or in virologic failure (2 consecutive viral loads with more than 1000 copies/ml). Exclusion Criteria: Patients with a viral load of less than 1000 copies/ml. Patients presenting for care having started treatment for systemic mycoses (amphotericin B or azoles) and tuberculosis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>All enrolled patients will be included in this arm of the study, patients will be administered all rapid diagnostic tests as part of their diagnostic work-up (this will constitute the main intervention of the study) | Diagnostic Test: Histoplasma Urine Antigen Lateral Flow Antigen test<br>* Lateral Flow Antigen test for urine samples to detect Histoplasma capsulatum disseminated disease<br>Diagnostic Test: Cryptococcal Lateral Flow Antigen test<br>* Lateral Flow Antigen test for serum or cerebrospinal fluid samples to detect Cryptococcus sp meningitis or disseminated disease<br>Diagnostic Test: Tuberculosis-lipoarabinomannan Lateral Flow Antigen test<br>* Lateral Flow Antigen test for serum samples to detect Mycobacterium tuberculosus disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time until opportunistic infection treatment initiation | Amount of time in days from the diagnosis of the opportunistic infection until the initiation of the specific treatment for the detected infection | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AIDS-related mortality at 30 days | If a patient has died due to AIDS-related causes | 30 days | 
| AIDS-related mortality at 90 days | If a patient has died due to AIDS-related causes | 90 days | 
| Monthly incidence of histoplasmosis, cryptococcosis and tuberculosis | The amount of diagnosed cases of histoplasmosis, cryptococcosis and tuberculosis per amount of advanced HIV-patients seen every month in the study sites | Through study completion, an average of 1 year | 
| Time until antiretroviral treatment initiation | Days passed from a patient's HIV diagnosis until he is given antiretroviral treatment for the first time | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rapid Diagnostic Tests, Point-of-Care Systems