Intracellular Survival of Leishmania Species That Cause Visceral Leishmaniasis Is Significantly Reduced

Visceral leishmaniasis is now recognized as an opportunistic disease in individuals infected with human immu-nodeficiency 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 pro-mastigotes 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 efficacyofPIs to reduce the intracellular growthofLeishmaniaparasites is alsoobserved inMDMscoinfectedwith 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 in-fections. This phenomenon complicates the therapeuti