Prophylaxis of Visceral Leishmaniasis Relapses in HIV Co-infected Patients With Pentamidine: a Cohort Study
Condition: Visceral Leishmaniosis; HIV-infection/Aids
MeSH terms: HIV Infections; Leishmaniasis; Leishmaniasis, Visceral; Acquired Immunodeficiency Syndrome; Recurrence
Intervention: Pentamidine
Intervention description: Pentamidine isethionate 300 mg for one vial for intramuscular or intravenous route(1 mg of pentamidine isethionate is equivalent to 0.57 mg of pentamidine base)
Intervention MeSH terms: Pentamidine
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Secondary prophylaxis; Visceral leishmaniasis; Relapses; HIV co-infection; Pentamidine; Ethiopia

Summary:

      Visceral leishmaniosis (VL) is widely reported in Ethiopia, with about 30% of cases being
      associated with human immunodeficiency virus (HIV). In absence of antiretroviral treatment
      (ART), poor prognosis, high mortality and high relapse rates are characteristic of Ethiopian
      VL patients with HIV co-infection. Conversely, co-infection can be successfully managed via a
      combination of effective treatment of the initial episode, timely ART and prevention of
      relapses.

      Actually, until cellular immunity returns with ART, the patient is at risk of VL relapses,
      which can result in death, severe illness, reduced ART efficacy, drug-resistance and possibly
      transmission of drug-resistant Leishmania donovani. Patients most vulnerable to relapses are
      those with high levels of immunosuppression, with previous VL episodes, or with opportunistic
      infections (OIs). The most important factor to prevent relapses seems to be the clearance of
      visible parasites.

      Limited studies in Europe show that HIV co-infected patients may benefit from secondary
      prevention with antimonials (part of mainstay treatment for VL in Ethiopia) and pentamidine
      (PM), not used for VL treatment in Africa. Such maintenance treatment has not been studied in
      African VL, but the poor outcomes without secondary prevention highlight a need of better
      care to patients at risk of relapse.

      This prospective cohort study aims at documenting the patient's outcomes of secondary
      prophylaxis with PM in VL-HIV co-infection, in terms of time to relapse or death, safety and
      feasibility, before it can be considered for general use in Ethiopia. A placebo group is not
      included, due to the clear advantages of the intervention to the patient population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients diagnosed with Visceral Leishmaniosis (VL) during the recruitment period that
             are EITHER treated for VL relapse and have a documented negative test of cure (TOC),
             OR are treated for primary VL and have a documented CD4 <200 or WHO stage 4 disease
             during the recruitment period and have a documented negative TOC

          -  Patients treated for VL in the past with documented CD4 <200 or WHO stage 4 disease
             during the recruitment period AND documented negative TOC after the latest VL
             treatment and currently asymptomatic OR currently negative diagnostic test
             (microscopy)

          -  Patients agreeing to start or continue antiretroviral treatment (first or second line)

          -  Patients willing to provide written informed consent

        Exclusion Criteria:

          -  Patients with known hypersensitivity to pentamidine

          -  Patients with known renal failure

          -  Patients with diabetes mellitus (type I or II)

          -  Patients unlikely to attend follow-up visits/comply with study requirements

          -  Pregnant and lactating women

          -  Any other condition that could increase the risk of toxicity of pentamidine to such an
             extent outweighing the expected benefit (eg severe cardiac dysfunction).