Antiretroviral drugs saquinavir and ritonavir reduce inhibitory concentration values of itraconazole against Histoplasma capsulatum strains in vitro

Abstract

Recent studies have shown that some drugs that are not routinely used to treat fungalinfections have antifungal activity, such as protease inhibitor antiretroviral drugs. This studyinvestigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavirand ritonavir, and its combination with the antifungal itraconazole. The susceptibility assaywas performed according to Clinical and Laboratory Standards Institute guidelines. Allstrains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed min-imum inhibitory concentrations ranging from 0.125 to 1 g mL−1for both phases, and riton-avir presented minimum inhibitory concentrations ranging from 0.0312 to 4 g mL−1andfrom 0.0625 to 1 g mL−1for filamentous and yeast phase, respectively. Concerning the anti-fungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to0.125 g mL−1and from 0.0039 to 0.0312 g mL−1for the filamentous and yeast phase, respec-tively. The combination of saquinavir or ritonavir with itraconazole was synergistic againstH. capsulatum, with a significant reduction in the minimum inhibitory concentrations of bothdrugs against the strains (p < 0.05). These data show an important in vitro synergy betweenprotease inhibitors and itraconazole against the fungus H. capsulatum.