Parasite susceptibility to amphotericin B in failures of treatment for visceral leishmaniasis in patients coinfected with HIV type 1 and Leishmania infantum

Clin Infect Dis. 2009 Jan 15;48(2):e16-22. doi: 10.1086/595710.

Abstract

Background: Visceral leishmaniasis (VL) is an opportunistic infection that can occur among patients infected with human immunodeficiency virus type 1 (HIV-1) in areas where both infections are endemic. Highly active antiretroviral therapy has decreased the incidence of VL in southern Europe among HIV-1-infected patients, but VL is still observed among patients with low CD4 cell counts, and most coinfected patients receiving highly active antiretroviral therapy experienced relapse, despite initial treatment with liposomal amphotericin B.

Methods: Through long-term monitoring of VL in 10 patients with HIV-1 infection and/or AIDS, we compared parasite strains derived from primary and secondary episodes of VL. All the patients have received many courses of amphotericin B treatment and/or prophylaxis.

Results: Through molecular techniques, we have shown that secondary episodes of VL can be attributable to relapse (7 of 10 episodes) or reinfection (3 of 10). We developed an assay to measure amphotericin B susceptibility and found no evidence of decreased susceptibility among strains isolated from patients, some of whom were infected with the same isolate for up to 10 years.

Conclusions: This apparent absence of resistance, as determined by in vitro susceptibility testing, has important consequences and suggests that amphotericin B will remain a useful drug of choice against VL, even after repetitive treatments or prophylactic use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / virology
  • Amphotericin B / pharmacology*
  • Amphotericin B / therapeutic use
  • Animals
  • Antiprotozoal Agents / pharmacology*
  • Antiprotozoal Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Europe
  • Follow-Up Studies
  • HIV-1 / isolation & purification
  • Humans
  • Leishmania infantum / drug effects*
  • Leishmania infantum / isolation & purification
  • Leishmaniasis, Visceral / drug therapy*
  • Leishmaniasis, Visceral / parasitology
  • Parasitic Sensitivity Tests
  • Treatment Failure

Substances

  • Antiprotozoal Agents
  • Amphotericin B