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OBJECTIVE: To report a case of extreme hyperlipidemia associated with protease inhibitor–based antiretroviral therapy and review the relevant literature concerning lipid abnormalities with HIV infection and antiretroviral therapy.CASE SUMMARY: A 35-year-old HIV-infected man developed a serum cholesterol of 1472 mg/dL and fasting serum triglycerides of 8660 mg/dL after initiation of antiretroviral therapy consisting of ritonavir, saquinavir, nevirapine, and didanosine. All other medications had been stable during this time period and the abnormality resolved after discontinuation of antiretroviral therapy and initiation of lipid-lowering therapy. The elevated cholesterol and triglyceride concentrations did not recur when therapy was reinstituted with nelfinavir, saquinavir, nevirapine, and didanosine. The hyperlipidemia then was attributed to ritonavir.DISCUSSION: Lipid abnormalities are common in patients with HIV infection and usually consist of hypocholesterolemia and moderate hypertriglyceridemia. Hypercholesterolemia and hypertriglyceridemia have been reported with ritonavir and, less commonly, with other currently available protease inhibitors. Some cases of ritonavir-associated hyperlipidemia have been extreme. Although an association between hyperlipidemia and clinical consequences such as pancreatitis and atherosclerotic disease has not been well described with protease inhibitor therapy, pancreatitis is common in HIV-infected patients. It is possible that in some cases, protease inhibitor–induced hypertriglyceridemia may contribute to the development of pancreatitis.CONCLUSIONS: Optimal management of lipid abnormalities in HIV-infected patients is controversial. The potential benefit of reducing the incidence of pancreatitis and atherosclerotic events must be weighed against the risk of intolerance, toxicity, and drug interactions.

OBJECTIVE: To evaluate a new enzyme-linked immunosorbent assay (ELISA) for amphotericin B in serum samples. Results are compared with those obtained by HPLC and bioassay.DESIGN: Comparison of results obtained by ELISA, HPLC, and bioassay.METHODS: We developed a new ELISA using a polyclonal rabbit antibody to measure serum amphotericin B concentrations. Blinded samples of amphotericin B in concentrations of 0.15–78 μg/mL were prepared in human serum and assayed simultaneously by the ELISA, HPLC, and bioassay. The results of each assay were derived from standard curves and evaluated by using the Table Curve 2D computer program. These data were compared by using correlation analysis with evaluation of Pearson's correlation coefficient by Student's t-est.RESULTS: ELISA and bioassay compared favorably at amphotericin B concentrations of 0.3–20 μg/mL with a correlation coefficient of r = 0.993, while ELISA and HPLC compared with a correlation coefficient of r = 0.944. The average coefficient of variation over the range 0.3–20.0 μg/mL was 28% ± 7% for HPLC, 26% ± 9% for ELISA, and 13% ± 4% for bioassay. Comparison of all three assays revealed the highest correlation with the ELISA assay (r = 0.998) for the range of concentrations (0.3–20 μg/mL) routinely achieved. Samples containing concentrations in excess of 20 μg/mL could be diluted. Desiccation for concentrations less than 0.3 μg/mL was not tested.CONCLUSIONS: The determination of serum amphotericin B concentrations by ELISA gave results similar to those obtained by a bioassay and HPLC technique. Although variability appears greater with ELISA, the ease of performing this assay expedites the evaluation of many samples. Finally, this assay may allow the determination of amphotericin B concentrations from lipid formulations without interference from coadministered antibacterials or azole antifungals.

OBJECTIVE: To review the role of itraconazole as oral therapy for the major infections caused by Aspergillusspp.: allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis.DATA SOURCES: A MEDLINE search of articles published in the English language between 1986 and 1993 was used to identify relevant citations, including review articles. In addition, a search of the published abstracts of the past two Interscience Conferences on Antimicrobial Agents and Chemotherapy (ICAAC) was performed.STUDY SELECTION: Clinical trials that evaluated itraconazole therapy in either allergic bronchopulmonary aspergillosis, aspergilloma, or invasive aspergillosis were critically reviewed. Trials were evaluated based upon entry criteria for the diagnosis of each type of aspergillosis, risk factors for the development of aspergillosis (neutropenia, transplant recipient, hematologic malignancy), prior antifungal chemotherapy, and dose and duration of itraconazole therapy.DATA SYNTHESIS: Overall, the clinical trials of itraconazole therapy for aspergillosis are limited and of variable quality. In the treatment of allergic bronchopulmonary aspergillosis, itraconazole has been reported to prompt a reduction in corticosteroid dosage in selected patients. There have been no controlled trials of itraconazole as treatment for aspergilloma, but data from several open-label trials suggest that this agent may be of clinical benefit in aspergilloma, primarily as an alternative to surgery. The use of itraconazole for invasive aspergillosis has been evaluated in several trials, most often in patients who were intolerant to amphotericin B treatment. Response to oral itraconazole has generally been promising.CONCLUSIONS: Although itraconazole offers promise for oral therapy against infections caused by Aspergillusspp., it should not presently be regarded as primary therapy for any of these diseases. Amphotericin B, in doses ranging from 1 to 1.5 mg/kg to a total dose of 1.5–4.0 g, should remain the treatment of choice in both aspergilloma and invasive aspergillosis. Itraconazole use should be restricted to patients who experience severe toxicity with amphotericin B therapy. Corticosteroids continue to be first-line therapy for allergic bronchopulmonary aspergillosis, with the use of itraconazole reserved for those patients who would benefit from a reduction in corticosteroid dose.