SALIVA AND ANTICANDIDAL DEFENSE MECHANISMS IN HIV/AIDS

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DESCRIPTION: This proposal will test the hypotheses that alterations in salivary gland function are associated with the progression of HIV infection and that such alterations in salivary gland function predispose to oral candidiasis. Secondly, with increasing severity of HIV infection, patients develop Sjogren's Syndrome-like features. The study will draw upon a patient population that has been staged into nine clinical categories and detailed medical and treatment histories are available for each subject. Parotid and submandibular/sublingual gland function will be assessed at baseline and at two additional times points, 18 months apart. Candida status will be determined by yeast counts and cytological smears of oral mucosa. Data will be analyzed for correlation between key host defense components in saliva and the stage of HIV infection, as well as with regard to progression of HIV disease and susceptibility to oral candidiasis at any given stage of HIV disease. The proposed study will provide fundamental insights into the dysregulation of the oral immune system which is at the core of oral problems in individuals who are HIV+ and have Sjogren's Syndrome. It will also provide an understanding of the role of salivary gland function in the predisposition to candidiasis in such patients and may lead to therapeutic approaches that may improve the quality of life for these individuals. The specific aims are: Specific Aim 1: Determine cross-sectional and longitudinal salivary gland changes (salivary flow rate, sialochemistry, and anti-HIV components) during the different stages of HIV infection. Such a systematic study of salivary gland function with progression of HIV infection has not been completed in a large study group, previously. Specific Aim 2: Determine changes in salivary anti-candidal activities with the progression of HIV infection. This aim will test the hypothesis that the predisposition to Candida infection is due to changes in salivary anti-fungal activity. A direct correlation will be sought between impairment of salivary anti-candidal components and clinical candidal infection. The concentration and functional activity of histatins, lysozyme and lactoferrin will be evaluated. Specific Aim 3: Determine the similarities and differences in salivary gland function of HIV infected patients and Sjogren's Syndrome. This aim of the proposal will evaluate routine sialochemistry as well as salivary proinflammatory and anti-inflammatory cytokines in both HIV+ and Sjogren's Syndrome patients.