Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 26 June 2014; Volume 8 (Issue 6); e2869.; DOI:10.1371/journal.pntd.0002869
Diro EGJ, Lynen L, Ritmeijer KKD, Boelaert M, Hailu ADE, et al.
PLoS Negl Trop Dis. 26 June 2014; Volume 8 (Issue 6); e2869.; DOI:10.1371/journal.pntd.0002869
Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.
Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 11 September 2014; Volume 8 (Issue 9); DOI:10.1371/journal.pntd.0003132
Van der Bergh R, Van Ginderachter J, Schouppe E, Desimmie B, Hailu ADE, et al.
PLoS Negl Trop Dis. 11 September 2014; Volume 8 (Issue 9); DOI:10.1371/journal.pntd.0003132
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 14 September 2016; Volume 10 (Issue 9); DOI:10.1371/journal.pntd.0004880
Wassuna M, Njenga SN, Balasegaram M, Alexander N, Omollo R, et al.
PLoS Negl Trop Dis. 14 September 2016; Volume 10 (Issue 9); DOI:10.1371/journal.pntd.0004880
SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa.
Journal Article > ResearchFull Text
BMC Nutr. 1 January 2013; Volume 29 (Issue 1); DOI:10.1016/j.nut.2012.04.016
Dibari F, Bahwere P, Huerga H, Hailu ADE, Owino V, et al.
BMC Nutr. 1 January 2013; Volume 29 (Issue 1); DOI:10.1016/j.nut.2012.04.016
To develop a method for determining the acceptability and safety of ready-to-use therapeutic foods (RUTF) before clinical trialing. Acceptability was defined using a combination of three consumption, nine safety, and six preference criteria. These were used to compare a soy/maize/sorghum RUTF (SMS-RUTFh), designed for the rehabilitation of human immunodeficiency virus/tuberculosis (HIV/TB) wasted adults, with a peanut-butter/milk-powder paste (P-RUTF; brand: Plumpy'nut) designed for pediatric treatment.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 21 February 2019; DOI:10.1371/journal.pntd.0007132.
Diro EGJ, Edwards T, Ritmeijer KKD, Fikre H, Abongomera C, et al.
PLoS Negl Trop Dis. 21 February 2019; DOI:10.1371/journal.pntd.0007132.
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.
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.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 17 January 2019; Volume 13 (Issue 1); DOI:10.1371/journal.pntd.0006988
Diro EGJ, Blesson S, Edwards T, Koert R, Ritmeijer KKD, et al.
PLoS Negl Trop Dis. 17 January 2019; Volume 13 (Issue 1); DOI:10.1371/journal.pntd.0006988
BACKGROUND
Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment.
Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45–87%) in the unadjusted analysis, and 50% (95% CI 27–73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67–90%) and 67% (95% CI 48–82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32–78%) in the monotherapy arm, and 88% (95% CI 79–98%) in the combination arm.
No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication.
CONCLUSIONS/SIGNIFICANCE
The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa.
TRIAL REGISTRATION NUMBER
www.clinicaltrials.gov NCT02011958
Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment.
Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45–87%) in the unadjusted analysis, and 50% (95% CI 27–73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67–90%) and 67% (95% CI 48–82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32–78%) in the monotherapy arm, and 88% (95% CI 79–98%) in the combination arm.
No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication.
CONCLUSIONS/SIGNIFICANCE
The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa.
TRIAL REGISTRATION NUMBER
www.clinicaltrials.gov NCT02011958
Protocol > Research Protocol
Hailu ADE, Diro EGJ, Kolja S, Ritmeijer KKD, Yifru S, et al.
1 July 2018
General Objectives
The overall objective of this trial is to identify a safe and effective treatment for VL in HIV coinfected
patients.
Primary Objective:
To evaluate at day 29 assessment the efficacy of a combination regimen of AmBisome®
+
miltefosine and AmBisome®
monotherapy in Ethiopian co-infected HIV + VL patients.
Secondary Objectives:
1. To evaluate relapse-free survival at day 390 (after initial cure at day 29 or cure at day 58 after
extended treatment).
2. To assess safety of the regimens.
Other objectives:
1.To evaluate of viral load and CD4 count in all patients
2. To evaluate the pharmacokinetics of ARV, Ambisome and miltefosine and immune function
markers in a subset of patients
The overall objective of this trial is to identify a safe and effective treatment for VL in HIV coinfected
patients.
Primary Objective:
To evaluate at day 29 assessment the efficacy of a combination regimen of AmBisome®
+
miltefosine and AmBisome®
monotherapy in Ethiopian co-infected HIV + VL patients.
Secondary Objectives:
1. To evaluate relapse-free survival at day 390 (after initial cure at day 29 or cure at day 58 after
extended treatment).
2. To assess safety of the regimens.
Other objectives:
1.To evaluate of viral load and CD4 count in all patients
2. To evaluate the pharmacokinetics of ARV, Ambisome and miltefosine and immune function
markers in a subset of patients
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 26 October 2010; Volume 4 (Issue 10); DOI:10.1371/journal.pntd.0000709
Hailu ADE, Musa AM, Wasunna M, Balasegaram M, Yifru S, et al.
PLoS Negl Trop Dis. 26 October 2010; Volume 4 (Issue 10); DOI:10.1371/journal.pntd.0000709
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.
Protocol > Research Protocol
Hailu ADE
1 October 2014
General Objectives
The overall objective of this trial is to identify a safe and effective treatment for VL in HIV coinfected
patients.
Primary Objective:
To evaluate at day 29 assessment the efficacy of a combination regimen of AmBisome® +
miltefosine and AmBisome® monotherapy in Ethiopian co-infected HIV + VL patients.
Secondary Objectives:
1. To evaluate relapse-free survival at day 390 (after initial cure at day 29 or cure at day 58 after
extended treatment).
2. To assess safety of the regimens.
Other objectives:
1.To evaluate of viral load and CD4 count in all patients
2. To evaluate the pharmacokinetics of ARV, Ambisome and miltefosine and immune function
markers in a subset of patients
The overall objective of this trial is to identify a safe and effective treatment for VL in HIV coinfected
patients.
Primary Objective:
To evaluate at day 29 assessment the efficacy of a combination regimen of AmBisome® +
miltefosine and AmBisome® monotherapy in Ethiopian co-infected HIV + VL patients.
Secondary Objectives:
1. To evaluate relapse-free survival at day 390 (after initial cure at day 29 or cure at day 58 after
extended treatment).
2. To assess safety of the regimens.
Other objectives:
1.To evaluate of viral load and CD4 count in all patients
2. To evaluate the pharmacokinetics of ARV, Ambisome and miltefosine and immune function
markers in a subset of patients
Journal Article > ResearchFull Text
Clin Infect Dis. 13 September 2017; Volume 66 (Issue 3); DOI:10.1093/cid/cix807
Diro EGJ, Ritmeijer KKD, Boelaert M, Alves F, Mohammed R, et al.
Clin Infect Dis. 13 September 2017; Volume 66 (Issue 3); DOI:10.1093/cid/cix807
We have conducted a single-arm trial evaluating monthly pentamidine secondary prophylaxis (PSP) to prevent visceral leishmaniasis (VL) relapse in Ethiopian HIV-patients. Outcomes at 12 months of PSP have been previously reported, supporting PSP effectiveness and safety. However, remaining relapse-free after PSP discontinuation is vital. We now report outcomes and associated factors for a period of upto 2.5 years after initiating PSP, including one year follow-up after PSP discontinuation.