The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia: A retrospective cohort study

Autor:	Johan van Griensven, Koert Ritmeijer, Ermias Diro, Alan de Lima Pereira, Charles Abongomera, Jozefien Buyze, Kolja Stille, Fareed Ahmed
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	0301 basic medicine RNA viruses Male Physiology HIV Infections Pathology and Laboratory Medicine 0302 clinical medicine Immunodeficiency Viruses Zoonoses Immune Physiology Medicine and Health Sciences Public and Occupational Health Leishmaniasis Coinfection Mortality rate lcsh:Public aspects of medicine HIV diagnosis and management Middle Aged Vaccination and Immunization 3. Good health Infectious Diseases Treatment Outcome Medical Microbiology Viral Pathogens Viruses Tuberculosis Diagnosis and Management Leishmaniasis Visceral Drug Therapy Combination Female Pathogens medicine.drug Research Article Neglected Tropical Diseases Adult medicine.medical_specialty lcsh:Arctic medicine. Tropical medicine Combination therapy lcsh:RC955-962 Phosphorylcholine 030231 tropical medicine 030106 microbiology Immunology Antiprotozoal Agents Antiretroviral Therapy Microbiology 03 medical and health sciences Kala-Azar Young Adult Antiviral Therapy Diagnostic Medicine Internal medicine Amphotericin B Retroviruses medicine Parasitic Diseases Humans Microbial Pathogens Retrospective Studies Miltefosine Protozoan Infections business.industry Lentivirus Public Health Environmental and Occupational Health Organisms Biology and Life Sciences HIV Retrospective cohort study lcsh:RA1-1270 Odds ratio medicine.disease Tropical Diseases Regimen Visceral leishmaniasis Parasitology Preventive Medicine Ethiopia business Spleen
Zdroj:	PLoS Neglected Tropical Diseases, Vol 12, Iss 5, p e0006527 (2018) PLoS Neglected Tropical Diseases
ISSN:	1935-2735 1935-2727
Popis:	Background North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients. Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates remain high with the available antileishmanial drugs, especially when administered as monotherapy. We aimed to determine the initial effectiveness (parasitologically-confirmed cure) of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients. Methodology/Principal findings We conducted a retrospective cohort study at a Médecins Sans Frontières—supported health center in north-west Ethiopia. We included VL-HIV co-infected adults, treated for VL between January 2011 and August 2014, with AmBisome infusion (30 mg/kg total dose) and miltefosine orally for 28 days (100 mg/day). Proportions of initial treatment outcome categories were calculated. Predictors of initial parasitological failure and of death were determined using multivariable logistic regression. Of the 173 patients included, 170 (98.3%) were male and the median age was 32 years. The proportion of patients with primary VL (48.0%) and relapse VL (52.0%) were similar. The majority had advanced HIV disease (n = 111; 73.5%) and were on antiretroviral therapy prior to VL diagnosis (n = 106; 64.2%). Initial cure rate was 83.8% (95% confidence interval [CI], 77.6–88.6); death rate 12.7% (95% CI, 8.5–18.5) and parasitological failure rate 3.5% (95% CI, 1.6–7.4). Tuberculosis co-infection at VL diagnosis was predictive of parasitological failure (adjusted odds ratio (aOR), 8.14; p = 0.02). Predictors of death were age >40 years (aOR, 5.10; p = 0.009), hemoglobin ≤6.5 g/dL (aOR, 5.20; p = 0.002) and primary VL (aOR, 8.33; p = 0.001). Conclusions/Significance Initial parasitological failure rates were very low with AmBisome and miltefosine combination therapy. This regimen seems a suitable treatment option. Knowledge of predictors of poor outcome may facilitate better management. These findings remain to be confirmed in clinical trials. Author summary North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL treatment outcomes in HIV co-infected patients are associated with high initial treatment (parasitological) failure and recurrence rates after cure (relapse). With secondary chemoprophylaxis, the risk of relapse can be reduced. However, with the current VL treatment regimens, the initial parasitological failure rates remain high. In this study, we aimed to determine the initial effectiveness of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV patients in Ethiopia. We conducted a retrospective study using routine program data from a Médecins Sans Frontières—supported health center in north-west Ethiopia. We included 173 adult VL-HIV co-infected patients treated for VL with a combination of AmBisome and miltefosine. Initial cure rate was 83.8%, death rate 12.7% and parasitological failure rate 3.5%. Tuberculosis co-infection at VL diagnosis was predictive of initial parasitological failure. Predictors of death were age >40 years, hemoglobin ≤6.5 g/dL and primary VL. Initial parasitological failure rates were very low with AmBisome and miltefosine combination therapy. This regimen seems a suitable treatment option. Knowledge of predictors of poor outcome may facilitate better management. These findings remain to be confirmed in other studies.
Databáze:	OpenAIRE
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