Vietnam Cryptococcal Retention in Care Study Version 1.0

Study Overview
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Brief Summary
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It is hypothesized that implementing plasma CrAg screening in clinics providing routine HIV care will enable identification of Vietnamese adult patients with advanced HIV (CD4 ≤100 cells/μL) who have early cryptococcal disease, enable prompt preemptive treatment with high-dose fluconazole, and improve survival.

Detailed Description
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This is multicenter prospective cohort evaluation of the implementation of a cryptococcal antigen (CrAg) screening program in Vietnam. HIV-infected patients with CD4 ≤100 cells/μL who present for HIV care at outpatient clinics (OPCs) in Vietnam where CrAg screening is offered will be recruited into the study. Study participants will be screened for cryptococcal antigen using the Lateral Flow Assay (LFA) and followed up for 12 months with clinical assessments and the collection of routine and supplemental survey data. Those who are CrAg-positive, but have no features of central nervous system (CNS) disease, will be treated with high-dose fluconazole. Those with symptoms of CNS disease will be treated according to national guidelines. Survival, retention in care, and other clinical outcomes will be documented for patients who test CrAg-positive and are treated with fluconazole and those who test CrAg-negative.

Official Title
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Evaluation of a Public Health Strategy to Improve Survival of HIV Infected Patients

Conditions
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Meningitis, Fungal, Meningitis, Cryptococcal, Central Nervous System Fungal Infections, Central Nervous System Infections

Intervention / Treatment
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* Drug: Fluconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years Confirmed HIV infection using National Testing Algorithm CD4 ≤100 cells/μL Able to provide written informed consent Exclusion Criteria: History of prior CM Receipt of systemic antifungal medication for more than 4 consecutive weeks within the past 6 months Currently taking ART or history of ART for more than 4 weeks within the past year Known to be currently pregnant or planning to become pregnant during the study period

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CrAg(+) and CM(+)<br>Patients with symptoms of CNS disease will be treated according to Vietnam national guidelines for HIV/AIDS management. | Drug: Fluconazole<br>* HIV-infected patients with CD4 ≤100 cells/μL who present for HIV care at outpatient clinics (OPCs) in Vietnam where CrAg screening is offered will be recruited into the study. Study participants will be screened for cryptococcal antigen using the Lateral Flow Assay (LFA). Those who are CrAg-positive, but have no features of central nervous system (CNS) disease, will be treated with high-dose fluconazole.<br>|
| CrAg(+) and CM(-)<br>Patients with CrAg(+) and without CM symptoms will be treated with high-dose fluconazole. The initial dosage of fluconazole will be 900 mg taken each day for 2 weeks. This will be followed by fluconazole 450 mg orally each day for 8 weeks. Finally, maintenance treatment with fluconazole 200mg orally each (2 tablets of 100 mg procured especially for the study) day will continue until CD4 >200 cells/µL for at least 6 months. | Drug: Fluconazole<br>* HIV-infected patients with CD4 ≤100 cells/μL who present for HIV care at outpatient clinics (OPCs) in Vietnam where CrAg screening is offered will be recruited into the study. Study participants will be screened for cryptococcal antigen using the Lateral Flow Assay (LFA). Those who are CrAg-positive, but have no features of central nervous system (CNS) disease, will be treated with high-dose fluconazole.<br>|
| CrAg negative<br>Patients with CrAg negative results will be managed as other HIV positive patients according to the national guidelines | Drug: Fluconazole<br>* HIV-infected patients with CD4 ≤100 cells/μL who present for HIV care at outpatient clinics (OPCs) in Vietnam where CrAg screening is offered will be recruited into the study. Study participants will be screened for cryptococcal antigen using the Lateral Flow Assay (LFA). Those who are CrAg-positive, but have no features of central nervous system (CNS) disease, will be treated with high-dose fluconazole.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six (6) and (12) month all-cause and CM-related mortality among patients who screen CrAg-positive and CrAg-negative |  | Up to 12 months after recruitment | 
| Proportion of all patients tested for plasma CrAg who have positive results |  | Up to 12 months after recruitment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients with HIV-related hospitalizations at 6 and 12 months |  | 12 months after recruitment | 
| Percent of patients with new AIDS-defining OIs/conditions at 6 and 12 months |  | 12 months after recruitment | 
| Causes of death |  | 12 months after recruitment | 
| Six (6) and (12) month retention among patients who screen CrAg-positive and CrAg-negative |  | 12 months after recruitment | 
| Percentage of patients with CD4≤ 100 cells/μL who are lost to follow-up or have incomplete documentation |  | 12 months after recruitment | 
| % of patients with no documented clinic visit 30, 60, and 90 days after date of the scheduled clinic appointment |  | 12 months after recruitment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, cryptococcal meningitis, AIDS, Fluconazole