Candida and candidiasis in HIV-infected subjects. Where commensalism, opportunistic behavior and frank pathogenicity lose their borders

In this era of efficacious antiretroviral therapy and consequent immune-reconstitution, oropharyngeal and oesophageal candidiasis (OPC and OEC) still remain two clinically relevant presentations in the global HIV setting. Both diseases are predominantly caused by Candida albicans, a polymorphic fungus which is a commensal microbe in the healthy subject but can become an aggressive pathogen in a debilitated host. Actually, C.albicans commensalism is not the result of a benign behavior of one of the many components of human microbiota, but rather the result of host's potent innate and adaptive immune responses that restrict the growth of a potentially dangerous microrganism on the epithelia. An important asset guarding against the fungus is the Th17 functional subset of T helper cells. The selective loss of these cells with the progression of HIV infection causes the decay of fungal containment on the oral epithelium and allows C.albicans to express its pathogenic potential. An important part of this potential is represented by mechanisms to evade host immunity and enhance inflammation and immunoactivation. In C.albicans these mechanisms are mostly incorporated into, and expressed by characteristic morphogenic transitions such as the yeast to hyphal growth and the white to opaque switch. In addition, HIV infection generates an 'environment' selecting for overexpression of the virulence potential by the fungus, particularly concerning the secretion of aspartyl proteinases (Sap). These enzymes can degrade critical host defense components such as complement and epithelial defensive proteins such as histatin-5 and E-cadherin. It appears that part of this enhanced Candida virulence could be induced by the binding of the fungus to HIV and/or induced by HIV proteins such as GP160 and tat. Both OPC and OEC can be controlled by old and new antimycotics, but in the absence of host collaboration, anticandidal therapy may become in the long run ineffective. For these reasons, new therapeutics targeting virulence factors such and specific immune interventions are being addressed. Among these new approaches, vaccination is a promising one. Two subunit vaccines based on antigens dominantly expressed by C.albicans in vivo, i.e. the Als3 adhesin and sap2, have recently undergone Phase 1 clinical trials. Overall, studies of Candida and candidiasis in the HIV+ subject, while certainly contributing to a more effective control of the microorganism, and may also provide useful information on HIV-host relationship itself that can assist the fight against the virus.