title: Effect of HIV protease inhibitors on New World Leishmania.
abstract: The incidence of HIV/Leishmania co-infection decreases after antiretroviral drug therapy; therefore, the in vitro and in vivo activity of three antiretroviral drugs against Leishmania (Viannia) braziliensis and L. (L.) amazonensis was evaluated. Different concentrations of indinavir (IDV), atazanavir (ATV), and ritonavir (RTV) were added to promastigote cultures, and the 50% inhibitory concentration (IC50) was determined. IDV and RTV were also evaluated against intracellular amastigotes, and the Infection Index determined. BALB/c mice, infected with L. (L.) amazonensis in the left footpad, were treated orally with IDV and RTV for 30 days, and monitored by measuring the footpad thickness and parasite load of regional lymph nodes and spleen. For promastigotes, IDV exhibited an IC50 value of 100 μM against L.(L.) amazonensis. The RTV IC50 for L. (L.) amazonensis and L. (V.) braziliensis were 40 and 2.3 μM, respectively, and the ATV IC50 for L. (V.) braziliensis was 266 μM. For intracellular amastigotes, IDV (25, 50, and 100 μM) significantly decreased the Infection Index of L. (L.) amazonensis (56.8%, 47.9%, and 65.0%) and L. (V.) braziliensis (37.8%, 48.7%, and 43.2%). RTV (12.5, 25, and 50 μM) decreased the infection index of L. (L.) amazonensis by 26.3%, 42.4%, and 44.0%, and that of L. (V.) braziliensis by 27.6%, 37.3%, and 39.2%. Antiretroviral-treated mice had a significant reduction in footpad thickness after the third week of IDV and after the fifth week of RTV treatment. However, there was no reduction in parasite load. These results suggest that IDV and RTV have anti-Leishmania activity, but only in higher concentrations.
authors.affiliation: Departamento de Análises Clínicas e Biomedicina, Universidade Estadual de Maringá, PR, Brazil. igdemarchi2@uem.br
authors.forename: Izabel G
authors.initials: IG
authors.lastname: Demarchi
authors.forename: Thaís G V
authors.initials: TG
authors.lastname: Silveira
authors.forename: Izabel C P
authors.initials: IC
authors.lastname: Ferreira
authors.forename: Maria V C
authors.initials: MV
authors.lastname: Lonardoni
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D004305:Dose-Response Relationship, Drug; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019469:Indinavir / Q000008:administration & dosage / Q000627:therapeutic use; D007891:Leishmania / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000981:Antiprotozoal Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019469:Indinavir; D000666:Amphotericin B; D019438:Ritonavir