Oropharyngeal
candidiasis is one of the first and most commonly reported
opportunistic infections of untreated
AIDS patients. With the introduction of the new
antiviral HAART therapy, including
HIV protease inhibitors, this mucocutaneous
infection is nowadays only rarely observed in treated patients. It was recently shown that
HIV protease inhibitors have a direct attenuating effect on Candida albicans secreted
aspartic proteinases (Saps), an investigation prompted by the fact that both Sap and
HIV protease belong to the superfamily of
aspartic proteinases and by the observation that mucocutaneous
infections sometimes resolve even in the absence of an immunological improvement of the host. As these Saps are important fungal
virulence factors and play a key role in adhesion to human epithelial cells we tried to assess the effect of the
HIV protease inhibitors Ritonavir,
Indinavir and
Saquinavir on fungal adhesion to these cells. The effect on phagocytosis by polymorphonuclear leukocytes was also assessed.
Ritonavir was found to be the most potent inhibitor of fungal adhesion. A dose-dependent inhibition of adhesion to epithelial cells was found already at 0.8 microM and was significant at 4 microM or higher, at 500 microM the inhibition was about 55%.
Indinavir and
Saquinavir inhibited significantly at 4 microM or 20 microM, respectively; at 500 microM the inhibition was 30% or 50%. In contrast, no
protease inhibitor was able to modulate phagocytosis of Candida by polymorphonuclear leukocytes. In conclusion, inhibition of Saps by
HIV protease inhibitors may directly help to ease the resolution of mucosal
candidiasis. In future, derivatives of
HIV protease inhibitors, being more specific for the fungal Saps, may form an alternative in the treatment of mucosal
candidiasis insensitive to currently available antimycotics.