TABLE 6.

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

HIV PI	Main findings	Reference(s)
In vitro
Ritonavir, indinavir, saquinavir	All three inhibited Sap2 activity. Only saquinavir was fungicidal, but only at high doses.	80
Indinavir	Indinavir 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, nelfinavir	Ritonavir 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, nelfinavir	All 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, indinavir	Both inhibited Sap2 activity. Saquinavir strongly attenuated tissue damage in an in vitro RHE model of oral candidiasis.	117
Indinavir, ritonavir	Neither had an antifungal effect.	55, 56
Ritonavir, indinavir, saquinavir	All three inhibited C. albicans adhesion to human epithelial cells; ritonavir was the most potent. None modulated phagocytosis of Candida.	10
In vivo models
Indinavir, ritonavir	Both inhibited Sap2 activity. Both exerted a therapeutic effect in an estrogen-dependent rat vaginitis model.	29
Indinavir, nelfinavir, ritonavir	The anti-Sap effect of PI-HAART was associated with clinical resolution of oral candidiasis in HIV-positive patients.	30