Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia.

Ermias Diro,Raymond Omollo,Fabiana Alves,Brian Mutinda,Koert Ritmeijer,Johan Van Griensven,Asrat Hailu,Jorge Alvar,Neal Alexander,Charles Abongomera,Aderajew Kibret,Monique Wasunna,Helina Fikre,Eduard E Zijlstra,Peninah Soipei,Clélia Bardonneau,Séverine Blesson,Tansy Edwards

doi:10.1371/journal.pntd.0007132

Abstract

BackgroundThe long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited.MethodsA prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 months. Patients with CD4 cell counts below 200/μL at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count ≥200 cells/μL were followed without secondary prophylaxis. Compliance, safety and relapse-free survival, using Kaplan-Meier analysis methods to account for variable time at risk, were summarised. Risk factors for relapse or death were analysed.ResultsFifty-four HIV patients were followed. The probability of relapse-free survival at one year was 50% (95% confidence interval [CI]: 35–63%): 53% (30–71%) in 22 patients with CD4 ≥200 cells/μL without pentamidine prophylaxis and 46% (26–63%) in 29 with CD4 <200 cells/μL who started pentamidine. Three patients with CD4 <200 cells/μL did not start pentamidine. Amongst those with CD4 ≥200 cells/μL, VL relapse was an independent risk factor for subsequent relapse or death (adjusted rate ratio: 5.42, 95% CI: 1.1–25.8). Except for one case of renal failure which was considered possibly related to pentamidine, there were no drug-related safety concerns.ConclusionThe relapse-free survival rate for VL patients with HIV was low. Relapse-free survival of patients with CD4 count <200cells/μL given pentamidine secondary prophylaxis appeared to be comparable to patients with a CD4 count ≥200 cells/μL not given prophylaxis. Patients with relapsed VL are at higher risk for subsequent relapse and should be considered a priority for secondary prophylaxis, irrespective of their CD4 count.

Highlights

When visceral leishmaniasis (VL) occurs in HIV patients, it presents several challenges [1]
Patients with CD4 cell counts below 200/μL at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count 200 cells/μL were followed without secondary prophylaxis
Long term outcomes of VL in HIV infected patients org for researchers who meet the criteria for access to confidential data

Summary

Introduction

When visceral leishmaniasis (VL) occurs in HIV patients, it presents several challenges [1] These include changes in clinical manifestations that may result in delayed diagnosis; changes in immunological response to the infection that affect the performance of diagnostic tools; and poor treatment response, in terms of low initial cure, relapse and mortality, due mainly to the combined effects of both infections causing profound immunosuppression [2,3]. The anti-leishmanial medicines available cannot completely eradicate the Leishmania parasites from the body [4] Even those patients who are declared parasitologically cured at the end of treatment are, in reality, left with some parasites in the tissues that are not undetectable by microscopy [5]. Use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited

Objectives

Methods

Conclusion