title: Use of Pentamidine As Secondary Prophylaxis to Prevent Visceral Leishmaniasis Relapse in HIV Infected Patients, the First Twelve Months of a Prospective Cohort Study.
abstract: BACKGROUND
  Visceral 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.
  
  
  METHODS
  A 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 4 mg/kg pentamidine-isethionate diluted in normal-saline were started for 12 months. All received antiretroviral therapy (ART). Time-to-relapse or death was the primary end point.
  
  
  RESULTS
  Seventy-four patients were included. The probability of relapse-free survival at 6 months 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 ≤ 50 cells/μl, 5/7 (71.4%) than those with counts above 200 cells/μl, 2/12 (16.7%), (p = 0.005).
  
  
  CONCLUSIONS
  Pentamidine 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.
authors.affiliation: University of Gondar, Gondar, Ethiopia; Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Ermias
authors.initials: E
authors.lastname: Diro
authors.affiliation: Médecins sans Frontières, Amsterdam, The Netherlands.
authors.forename: Koert
authors.initials: K
authors.lastname: Ritmeijer
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: Boelaert
authors.affiliation: Drugs for Neglected Diseases Initiative, Geneva, Switzerland.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Alves
authors.affiliation: University of Gondar, Gondar, Ethiopia.
authors.forename: Rezika
authors.initials: R
authors.lastname: Mohammed
authors.affiliation: Médecins sans Frontières, Abdurafi, Ethiopia.
authors.forename: Charles
authors.initials: C
authors.lastname: Abongomera
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ravinetto
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Maaike
authors.initials: M
authors.lastname: De Crop
authors.affiliation: University of Gondar, Gondar, Ethiopia.
authors.forename: Helina
authors.initials: H
authors.lastname: Fikre
authors.affiliation: Médecins sans Frontières, Abdurafi, Ethiopia.
authors.forename: Cherinet
authors.initials: C
authors.lastname: Adera
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Colebunders
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Harry
authors.initials: H
authors.lastname: van Loen
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Menten
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Lynen
authors.affiliation: School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Asrat
authors.initials: A
authors.lastname: Hailu
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: van Griensven
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000328:Adult; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D008297:Male; D010419:Pentamidine / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012008:Recurrence
chemical_list: D000981:Antiprotozoal Agents; D010419:Pentamidine