Intracellular Survival of Leishmania Species That Cause Visceral Leishmaniasis Is Significantly Reduced by HIV-1 Protease Inhibitors
2008
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 sensitivestrain,thussuggestingthatresistancetoSbVdoesnotresultincross-resistancetoPIs.Importantly,the efficacyofPIstoreducetheintracellulargrowthofLeishmaniaparasitesisalsoobservedinMDMscoinfectedwith HIV-1. In the wake of the extensive and rapid expansion of the worldwide AIDS pandemic, several infectious diseases have developed into AIDS-associated opportunistic infections. This phenomenon complicates the therapeutic measures aimed at controlling HIV-1, the causative agent of AIDS, and the various opportunistic pathogens
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