Although Candida albicans infections in humans are increasingly frequent, our understanding of the host-parasite relationship is limited. The secreted aspartic proteinase of C. albicans was first described in 1965 and has proved to be a major factor in virulence. This enzyme belongs to the class of aspartic proteinases which includes pepsin and renin in humans. Although found in some fungi, secreted aspartic proteinase is rare in these organisms. While the existence of several isoenzymes may not be fully established, it is now obvious that at least seven different genes encode for secreted aspartic proteinase. Within Candida cells it is located in membrane-bound vesicles. Upon fusion of these subcellular structures within the plasma membrane, the enzyme is released to the environment. In the context of human mucosal diseases it is responsible both for adhesion and invasion. Strains from HIV-infected patients with oral candidosis generally exhibit higher enzymatic activity than control strains. In future secreted aspartic proteinase may prove a prime target for new types of antimycotics.

The introduction of HIV protease inhibitors was accompanied by reduction in HIV-associated opportunistic infections. Therefore, we performed a retrospective study of HIV-infected patients to evaluate the effects of therapy with an HIV protease inhibitor (PI) on oral candidosis. This was of special interest, because an important virulence factor of Candida albicans is the secreted aspartic protease (SAP), which is assigned to the same class of aspartic proteases as HIV protease. Sixty-two patients were examined five times over a period of 2 years. There was a hint at a difference in the frequencies of C. albicans carrier state and manifest oral candidosis in favour of treatment with a PI. In addition, loss of Candida colonization and manifest oral candidosis was observed only in patients with elevation of CD4 cells upon PI. This might explain the effect, which also might go back to a direct inhibition of yeast SAP.

A 38-year-old woman infected with human immunodeficiency virus (HIV) presented with persistent oral candidosis in which non-albicans Candida strains were the predominant yeasts in most of the examinations performed over a period of 6 years. Oral treatment with fluconazole had no effect on clinical signs of oral candidosis. In 8 of a total of 11 specimens, Candida glabrata, Candida parapsilosis and Candida tropicalis were at least suspected as the causative pathogens of oral candidosis. The non-response to fluconazole in our patient could be explained by in vitro resistance to fluconazole of detected Candida glabrata and Candida tropicalis isolates.

A 45-year-old human immunodeficiency virus (HIV)-infected patient has suffered for a period of 4 years from recurrent and, later on, persistent oral pseudomembranous candidosis. The Candida isolates proved to be resistant to azole derivates in vitro and in vivo. Treatment with amphotericin B parenterally was successful in February 1996, but had to be stopped when chemotherapy for lymphoma was started. In August 1996, the patient showed a shift from the pseudomembranous to the erythematous type of oral candidosis; antiretroviral combination therapy including the HIV protease inhibitor saquinavir had been started 4 months previously. In July 1997, the patient was still suffering from a persistent oral candidosis of the erythematous type.

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