Recurrent Visceral Leishmaniasis in HIV Co-Infection

New And Recurrent Visceral Leishmaniasis in HIV Co-Infected Ethiopian Patients: a Cohort Study

The aim is (1) to better understand the underlying causes and predispositions for relapse and parasite persistence in visceral leishmaniasis (VL) patients living with HIV and (2) to improve treatment monitoring of this target group in Ethiopia

Prospective and retrospective observational cohort study

Main objective

- To identify the key host and pathogen factors that contribute to active chronicity (=recurrent or chronic parasite presence in blood, tissue and/or skin in combination with clinical symptoms) in VL/HIV patients in northern Ethiopia

Specific objectives

• To describe the VL/HIV patients by level of chronicity using routine clinical and laboratory data
• To monitor parasite presence by molecular diagnostic in peripheral blood and - if available - tissue aspirates before, during, after treatment as well as during follow-up by level of disease chronicity
• To broadly characterize the underlying HIV co-infection and potential of ART resistance by level of disease chronicity
• To genotype the Leishmania parasites by level of disease chronicity to assess re-infection, recrudescence, drug resistance, and quiescence/virulence
• To identify other concomitant (latent) co-infections (TB, malaria, intestinal helminths, viral infections) and its impact on disease chronicity
• To study the level of exhaustion and immune checkpoint inhibition pathways, as potential therapy targets, by disease chronicity
• To assess the quality of life by a standardised questionnaire at admission and during follow-up

Exploratory objective:

• To study the persistence and quantity of parasites within the skin
• To study the stool microbiome of VL-HIV patients
• To assess the potential impact of secondary prophylaxis on relapse frequency, relapse intervals, relapse intensity, and exhaustion marker (compared with historical cohort/patients without secondary prophylaxis)

Inclusion Criteria:

1. VL-HIV infection 1.1. VL: microscopically confirmed parasite presence in spleen or bone marrow tissue at first episode or relapse; for known active chronic cases: decision to treat VL 1.2. HIV: confirmed viral infection (new or past)
2. ≥18 years

Exclusion Criteria:

1. Not willing to provide written informed consent
2. Not willing to adhere to the follow-up visits
3. Mentally or physically incapable to participate in the study (to the discretion of the treating physician)