Effect of HIV PIs on Sap activity and C. albicans virulence

HIV PIMain findingsReference(s)
In vitro
    Ritonavir, indinavir, saquinavirAll three inhibited Sap2 activity. Only saquinavir was fungicidal, but only at high doses. 80
    IndinavirIndinavir weakly inhibited Sap2 and reduced the amount of cell-bound and secreted proteinase. C. albicans viability and growth were markedly reduced. 83
    Ritonavir, indinavir, saquinavir, nelfinavirRitonavir and saquinavir inhibited Sap2 at micromolar concentrations, whereas indinavir and nelfinavir had no effect. Ritonavir and saquinavir also inhibited Sap proteins from C. tropicalis, C. parapsilosis, and C. lusitaniae. 168
    Ritonavir, indinavir, saquinavir, nelfinavirAll four specifically inhibited Sap1 to Sap3, but not Sap4 to Sap6. Ritonavir and saquinavir inhibited C. albicans adherence to epithelial cells, whereas indinavir had no effect. No effect on C. albicans viability. 15
    Saquinavir, indinavirBoth inhibited Sap2 activity. Saquinavir strongly attenuated tissue damage in an in vitro RHE model of oral candidiasis. 117
    Indinavir, ritonavirNeither had an antifungal effect. 55, 56
    Ritonavir, indinavir, saquinavirAll three inhibited C. albicans adhesion to human epithelial cells; ritonavir was the most potent. None modulated phagocytosis of Candida. 10
In vivo models
    Indinavir, ritonavirBoth inhibited Sap2 activity. Both exerted a therapeutic effect in an estrogen-dependent rat vaginitis model. 29
    Indinavir, nelfinavir, ritonavirThe anti-Sap effect of PI-HAART was associated with clinical resolution of oral candidiasis in HIV-positive patients. 30