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.


Journal

PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488

Informations de publication

Date de publication:
02 2019
Historique:
received: 21 09 2018
accepted: 06 01 2019
revised: 05 03 2019
pubmed: 23 2 2019
medline: 21 3 2019
entrez: 22 2 2019
Statut: epublish

Résumé

The 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. A 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. Fifty-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. The 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.

Sections du résumé

BACKGROUND
The 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.
METHODS
A 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.
RESULTS
Fifty-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.
CONCLUSION
The 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.

Identifiants

pubmed: 30789910
doi: 10.1371/journal.pntd.0007132
pii: PNTD-D-18-01439
pmc: PMC6400407
doi:

Substances chimiques

Antiprotozoal Agents 0
Pentamidine 673LC5J4LQ

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0007132

Subventions

Organisme : Medical Research Council
ID : MR/K012126/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R010161/1
Pays : United Kingdom

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Ermias Diro (E)

Leishmaniasis Research and Treatment Centre, University of Gondar, Gondar, Ethiopia.

Tansy Edwards (T)

MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Koert Ritmeijer (K)

Médecins sans Frontières, Amsterdam, The Netherlands.

Helina Fikre (H)

Leishmaniasis Research and Treatment Centre, University of Gondar, Gondar, Ethiopia.

Charles Abongomera (C)

Abdurafi Health Centre, Médecins sans Frontières, Ethiopia.

Aderajew Kibret (A)

Abdurafi Health Centre, Médecins sans Frontières, Ethiopia.

Clélia Bardonneau (C)

Research & Development Department, Drugs for Neglected Diseases initiative, Geneva, Switzerland.

Peninah Soipei (P)

Drugs for Neglected Diseases initiative, Nairobi, Kenya.

Brian Mutinda (B)

Drugs for Neglected Diseases initiative, Nairobi, Kenya.

Raymond Omollo (R)

Drugs for Neglected Diseases initiative, Nairobi, Kenya.

Johan van Griensven (J)

Institute of Tropical Medicine, Antwerp, Belgium.

Eduard E Zijlstra (EE)

Research & Development Department, Drugs for Neglected Diseases initiative, Geneva, Switzerland.

Monique Wasunna (M)

Drugs for Neglected Diseases initiative, Nairobi, Kenya.

Fabiana Alves (F)

Research & Development Department, Drugs for Neglected Diseases initiative, Geneva, Switzerland.

Jorge Alvar (J)

Research & Development Department, Drugs for Neglected Diseases initiative, Geneva, Switzerland.

Asrat Hailu (A)

Department of Microbiology, Immunology, and Parasitology, Addis Ababa University, Addis Ababa, Ethiopia.

Neal Alexander (N)

MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Séverine Blesson (S)

Research & Development Department, Drugs for Neglected Diseases initiative, Geneva, Switzerland.

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Classifications MeSH