Date Published: October 2, 2015
Publisher: Public Library of Science
Author(s): Ermias Diro, Koert Ritmeijer, Marleen Boelaert, Fabiana Alves, Rezika Mohammed, Charles Abongomera, Raffaella Ravinetto, Maaike De Crop, Helina Fikre, Cherinet Adera, Robert Colebunders, Harry van Loen, Joris Menten, Lutgarde Lynen, Asrat Hailu, Johan van Griensven, Hechmi Louzir. http://doi.org/10.1371/journal.pntd.0004087
Abstract: BackgroundVisceral leishmaniasis (VL) has become an important opportunistic infection in persons with HIV-infection in VL-endemic areas. The co-infection leads to profound immunosuppression and high rate of annual VL recurrence. This study assessed the effectiveness, safety and feasibility of monthly pentamidine infusions to prevent recurrence of VL in HIV co-infected patients.MethodsA single-arm, open-label trial was conducted at two leishmaniasis treatment centers in northwest Ethiopia. HIV-infected patients with a VL episode were included after parasitological cure. Monthly infusions of 4mg/kg pentamidine-isethionate diluted in normal-saline were started for 12months. All received antiretroviral therapy (ART). Time-to-relapse or death was the primary end point.ResultsSeventy-four patients were included. The probability of relapse-free survival at 6months and at 12 months was 79% and 71% respectively. Renal failure, a possible drug-related serious adverse event, occurred in two patients with severe pneumonia. Forty-one patients completed the regimen taking at least 11 of the 12 doses. Main reasons to discontinue were: 15 relapsed, five died and seven became lost to follow-up. More patients failed among those with a CD4+cell count ≤ 50cells/μl, 5/7 (71.4%) than those with counts above 200 cells/μl, 2/12 (16.7%), (p = 0.005).ConclusionPentamidine secondary prophylaxis led to a 29% failure rate within one year, much lower than reported in historical controls (50%-100%). Patients with low CD4+cell counts are at increased risk of relapse despite effective initial VL treatment, ART and secondary prophylaxis. VL should be detected and treated early enough in patients with HIV infection before profound immune deficiency installs.
Partial Text: Visceral leishmaniasis (VL) is a fatal-but treatable- disease caused by a protozoan belonging to the Leishmania donovani complex. While the Indian-subcontinent, East-Africa and Brazil share the major disease burden, it was long known as a rare pediatric disease in the Mediterranean basin. However, in the HIV-era, VL resurged in Southern Europe in adults with HIV co-infection  and has been a clinical challenge until highly-active antiretroviral therapy (ART) was introduced [2,3]. Today the co-infection is reported from 35 countries  and VL is an important opportunistic infection of HIV [5,6].
The probability of failure (relapse or death) from secondary VL chemoprophylaxis within 1 year was 29% which is lower than the 50% to 100% reported in case series without prophylaxis in Europe [7–11]. The annual probability of VL relapse was 56% in a cohort of patients with HIV on ART, but without secondary prophylaxis in northwest Ethiopia . In a meta-analysis of studies conducted in the L infantum region, the relapse rate was reduced from 67% to 31% with chemoprophylaxis . Our study endpoint was relapse and death, while only the relapse rate was reported from the other studies.