Predicting and evaluating outcome in oropharyngeal candidasis (OPC) in Aids

Oropharyngeal candidiasis (OPC) is the commonest opportunistic infection in HIV-infected individuals, and despite a number of existing modalities of treatment remains a cause of considerable morbidity. Fluconazole is the standard of treatment, but resistance is common. New treatments are required. The definition of outcome of treatment with existing and new modalities of treatment are ill-defined in both fluconazole-refractory and susceptible disease. The work described in this thesis has produced a clinical scoring system for the assessment of new treatment modalities, and better defined the symptomatology of fluconazole-refractory and susceptible disease. Fluconazole-refractory disease was found to have significantly greater oral coverage, number and frequency of symptoms and is seen in patients with lower CD4 cell counts compared with susceptible disease. Improvements in dysphagia and oral pain were the most significant symptom responses. No significant differences in mycological parameters (CFU) were seen in either group pre- or post-treatment.During the study period new HIV treatment (HAART) dramatically altered mortality and morbidity in the study cohort. The effect of the introduction of this treatment on the incidence of OPC is described. The reduction in incidence of OPC precluded firm conclusions with regard to the optimal susceptibility testing methods and full characterization of the pharmacokinetic-pathogen population dynamics for ketoconazole and itraconazole. In spite of this, this is the first attempt to utilise a population pharmacokinetic model and combine a modified pathogen population dynamic and pharmacokinetic approach to the treatment of OPC with itra and keto in AIDS.