Predicting Visceral Leishmaniasis in HIV Infected Patients

Study Overview
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Brief Summary
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In this cohort study, the investigators will study the asymptomatic period preceding the onset of active Visceral Leishmaniasis (VL) in HIV-infected individuals from VL endemic regions in Ethiopia as an avenue to develop an evidence-based screen and treat strategy to prevent progression to active VL.

Detailed Description
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HIV co-infection drastically increases the risk of developing active VL. Clinical outcomes are dire in immune-compromised patients even with the best available treatment, and relapse is frequent. The incubation period may provide an important window of opportunity for a pre-emptive screen an treat approach in HIV co-infected patients to prevent progression from infection to the active disease. However, no recommendations exist to date due to lack of solid evidence. It is not known which patients are at highest risk of disease progression, which role parasite/host/HIV factors play in the asymptomatic infection phase, and what the diagnostic values of existing Leishmania infection markers are. Such information is needed to develop a prognostic clinical tool for the detection of HIV patients at high risk of developing active VL. Therefore, the aim is to study the asymptomatic period preceding the onset of active VL in HIV-infected individuals from VL endemic regions in Ethiopia as an avenue to develop an evidence-based screen and treat strategy to prevent progression to active VL. This will be a prospective cohort study with one year of follow-up for patients who remain VL free. Patients developing active VL during the study period will be followed until the end of the study duration.

Official Title
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Predicting Visceral Leishmaniasis in HIV Infected Patients

Conditions
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Leishmaniasis, Visceral

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed HIV-positive Enrolled in HIV care at the study site Exclusion Criteria: Age under 18 years Diagnosis of active Visceral Leishmaniasis at enrolment Unlikely to seek health care again at this site during the next two years Not able or willing to provide informed consent. For patients not able to provide informed consent: No guardian available or willing to provide IC Medical emergency, underlying chronic medical condition, or other circumstances that make adherence to the study unlikely, or participation in the study medically inadvisable.

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 |
| --- | --- |
| HIV<br>HIV infected individuals residing in VL-endemic areas in Northern Ethiopia | Other: No intervention<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of asymptomatic Leishmania infection | The proportion of individuals with asymptomatic Leishmania infection at enrolment, among all enrolled participants | January 2018 | 
| Incidence rate of asymptomatic Leishmania infection | The number of individuals with newly diagnosed asymptomatic Leishmania infection per person-years at risk during follow-up, among participants without Leishmania infection at enrolment | January 2020 | 
| Evolution of Leishmania infection markers | The proportions of individuals with positive test results for the different Leishmania infection markers at each follow-up visit | January 2020 | 
| Incidence rate of active VL | The number of individuals who develop active VL per person-years at risk during follow-up, among all enrolled participants | January 2020 | 
| Risk factors for active VL | The association between the risk to develop active VL during follow-up and demographic/clinical characteristics as well as HIV/host immunity/Leishmania infection markers from baseline onwards | January 2020 | 
| Prognostic tool for active VL | A clinical decision algorithm, prioritizing and integrating identified risk factors, that is able to most efficiently predict the risk of developing active VL within 12 months | January 2021 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patterns in host immune markers for asymptomatic Leishmania infection | The association between asymptomatic Leishmania infection and the levels of the different host immune markers, among participants tested for host immune markers | January 2020 | 
| Evolution of host immune markers | The average levels of the different host immune markers at each follow-up visit | January 2020 | 
| Patterns in host immune markers for VL treatment failure | The association between the risk of VL treatment failure and the levels and evolution of the different host immune markers, among participants who develop active VL and receive VL treatment | January 2021 | 
| Patterns in host immune markers for VL relapse | The association between the risk of VL relapse and the levels and evolution of the different host immune markers, among participants who develop active VL | January 2021 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leishmaniasis, visceral, neglected, HIV, co-infection, asymptomatic, Ethiopia