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Opportunistic infections (OIs) are the leading cause of mortality and morbidity among HIV-positive subjects. The breadth of reports of the rare occurrence of OIs in HIV/AIDS has been increasing over the years and more recent studies have outlined the changing trends in the emergence of newer pathogens. Recent reports of the association of certain protozoans that normally do not infect sites other than their normal sites of localization have generated huge interest among scientists. The complete depression of the immune system, followed by the onset of OIs, especially due to protozoans, i.e. toxoplasmosis, isosporiasis, leishmaniasis, cyclosporosis, microsporidiosis and cryptosporidiosis, is not uncommon in AIDS. The immunologic and pathologic basis behind the susceptibility of immunodepressed individuals to these ‘non-site-specific parasites’ is likely to have a huge impact on HIV disease progression. Certain possible shortcomings in the immunologic armory of immunodeficient subjects, their failure to contain the establishment of these ‘uncommon’ agents in the human host and their significance in HIV disease progression are discussed. [ABSTRACT FROM AUTHOR]