title: Intracellular survival of Leishmania species that cause visceral leishmaniasis is significantly reduced by HIV-1 protease inhibitors.
abstract: Visceral leishmaniasis is now recognized as an opportunistic disease in individuals infected with human immunodeficiency virus type 1 (HIV-1). Although the usefulness of HIV-1 protease inhibitors (PIs) in antiretroviral regimens is well documented, little is known about their potential impact in the setting of Leishmania/HIV-1 coinfections. We now report that, although selected PIs do not inhibit the growth of Leishmania infantum promastigotes alone in culture, these drugs significantly inhibit the intracellular survival of parasites in phorbol myristate acetate-differentiated THP-1 macrophages and human primary monocyte-derived macrophages (MDMs). Furthermore, a field isolate of Leishmania donovani resistant to sodium stibogluconate (SbV), one of the drugs most commonly used to treat leishmaniasis, is equally susceptible to the tested PIs compared with a sensitive strain, thus suggesting that resistance to SbV does not result in cross-resistance to PIs. Importantly, the efficacy of PIs to reduce the intracellular growth of Leishmania parasites is also observed in MDMs coinfected with HIV-1.
authors.affiliation: Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Département de Biologie Médicale, Université Laval, Québec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Trudel
authors.forename: Ravendra
authors.initials: R
authors.lastname: Garg
authors.forename: Nadine
authors.initials: N
authors.lastname: Messier
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.forename: Marc
authors.initials: M
authors.lastname: Ouellette
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000502:physiology*; D007898:Leishmaniasis, Visceral / Q000469:parasitology*; D007928:Lethal Dose 50; D008264:Macrophages / Q000469:parasitology; D019888:Nelfinavir / Q000494:pharmacology; D019438:Ritonavir / Q000494:pharmacology; D019258:Saquinavir / Q000494:pharmacology
chemical_list: D017320:HIV Protease Inhibitors; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir