Parasitology Research

, Volume 115, Issue 10, pp 3881–3887 | Cite as

Antileishmanial activity of antiretroviral drugs combined with miltefosine

  • Sonya Costa
  • Marisa Machado
  • Cláudia Cavadas
  • Maria do Céu SousaEmail author
Original Paper


Co-infection of Leishmaniasis, a neglected tropical disease, with human immunodeficiency virus (HIV) has hindered treatment efficacy. In this study, we aim to evaluate the antileishmanial activity of two protease inhibitors (darunavir and atazanavir) and four reverse transcriptase inhibitors (tenofovir, efavirenz, neviraprine, and delavirdine mesylate) on Leishmania infantum. The activity of different antiretrovirals combinations and of antiretroviral with miltefosine, a drug used on leishmaniasis treatment, was also evaluated. Only two non-nucleoside reverse transcriptase inhibitors (NNRTIs) were active on L. infantum. Efavirenz showed the best antileishmanial activity on promastigotes cells with IC50 value of 26.1 μM followed by delavirdine mesylate with an IC50 value of 136.2 μM. Neviraprine, tenofovir, atazanavir, and darunavir were not active at the concentrations tested (IC50 > 200 μM). The efavirenz also showed high antileishmanial activity on intramacrophage amastigotes with IC50 of 12.59 μM. The interaction of efavirenz with miltefosine improved antileishmanial activity on promastigotes and intracellular amastigotes (IC50 values of 11. 8 μM and 8.89 μM, respectively). These results suggest that combined-therapy including efavirenz and miltefosine could be alternative options for treating Leishmaniasis and Leishmania/HIV co-infections.


Leishmania infantum Leishmania/HIV co-infection Efavirenz Delavirdine mesylate Miltefosine 



We would like to thank Professor Isabel Vitória Figueiredo, Faculty of Pharmacy of University of Coimbra, Débora Botura Scariot and Hélito Volpato, State University Maringá (UEM)-Brazil, for the technical support on isolation of intraperitoneal macrophages and Leishmania macrophage infection.

Work supported by FCT POCTI (FEDER) and COMPETE (PEst-C/SAU/LA000172013-2014).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Sonya Costa
    • 1
    • 2
  • Marisa Machado
    • 3
    • 4
  • Cláudia Cavadas
    • 2
    • 5
  • Maria do Céu Sousa
    • 2
    • 5
    Email author
  1. 1.Programme in Experimental Biology and Biomedicine, Centre for Neurosciences and Cell Biology, and Institute for Interdisciplinary ResearchUniversity of CoimbraCoimbraPortugal
  2. 2.CNC -Center for Neurosciences and Cell BiologyUniversity of CoimbraCoimbraPortugal
  3. 3.CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da SaúdeGandraPortugal
  4. 4.CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos GenéticosUniversidade do Porto, InBIOVairãoPortugal
  5. 5.Faculty of PharmacyUniversity of CoimbraCoimbraPortugal

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