HIV-1 protease inhibitors for treatment of visceral leishmaniasis in HIV-co-infected individuals

J. van Griensven, E. Diro, R. Lopez-Velez, M. Boelaert, L. Lynen, E. Zijlstra, J.C. Dujardin, A. Hailu

Research output: Contribution to journalA1: Web of Science-article

Abstract

The global prevalence of HIV is a major challenge for control of visceral leishmaniasis, a disseminated protozoan infection. In some east African regions, up to 40% of patients with visceral leishmaniasis are co-infected with HIV. Management of visceral leishmaniasis in such patients is complicated by treatment failures and relapses, even while patients are receiving standard antiretroviral therapy. In-vitro studies have consistently documented an inhibitory effect of specific HIV-1 protease inhibitors on leishmania parasites, and the underlying mechanism is partly explained. With the global scaling up of HIV treatment, HIV-1 protease inhibitors are increasingly becoming available for second-line HIV treatment in regions where visceral leishmaniasis and HIV are endemic. However, additional research is needed before HIV-1 protease inhibitors can be taken forward for clinical use against visceral leishmaniasis in HIV-infected patients. Since the effect of protease inhibitors against Leishmania species was generally observed at high drug concentrations, efficacy and dose-response relationships should be studied in animals before these drugs are used in clinical trials. More extensive studies of all available HIV protease inhibitors are needed, including investigation of drug interactions and emergence of drug-resistant parasites. In addition to exploring the full potential of current HIV-1 protease inhibitors against visceral leishmaniasis, leishmania-specific protease inhibitors should be developed.
Original languageEnglish
JournalLancet Infectious Diseases
Volume13
Issue number3
Pages (from-to)251-259
Number of pages9
ISSN1473-3099
DOIs
Publication statusPublished - 2013

Keywords

  • Protozoal diseases
  • Kala azar
  • Visceral
  • Leishmaniasis
  • Leishmania donovani
  • Leishmania infantum
  • Leishmania chagasi
  • Vectors
  • Sandflies
  • Phlebotomus argentipes
  • Co-infections
  • Viral diseases
  • HIV-1
  • AIDS
  • Control
  • Clinical management
  • Protease inhibitors
  • Treatment
  • Nelfinavir
  • Indinavir
  • Ritonavir
  • Saquinavir
  • Lopinavir
  • Atazanavir
  • Amprenavir
  • Fosamprenavir
  • Darunavir
  • Tipranavir
  • Review of the literature

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