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HIV/AIDS

Clinical Evidence of Interaction Between Itraconazole and Nonnucleoside Reverse Transcriptase Inhibitors in HIV-Infected Patients with Disseminated Histoplasmosis

Assistant Professor, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX; Thomas Street Health Center, Harris County Hospital District, Houston

Richard T Evans, MS

Clinical Research Coordinator III, Section of Infectious Diseases, Baylor College of Medicine; Thomas Street Health Center, Harris County Hospital District

Richard J Hamill, MD

Professor, Section of Infectious Diseases, Baylor College of Medicine; Michal E DeBakey Veterans Affairs Medical Center, Houston

Teddy Zerai, DPharm

Pharmacist, Thomas Street Health Center, Harris County Hospital District

Thomas P Giordano, MD

Assistant Professor, Section of Infectious Diseases, Baylor College of Medicine; Medical Director, Thomas Street Health Center, Harris County Hospital District

Reprints: Dr. Andrade, Thomas Street Health Center, 2015 Thomas St., Houston, TX 77009, fax 713/873-4047, randrade{at}bcm.tmc.edu

BACKGROUND: Itraconazole is the preferred drug for chronic maintenance therapy in HIV-infected patients with disseminated histoplasmosis. Unfortunately, few clinical data exist confirming a presumed interaction between itraconazole and nonnucleoside reverse transcriptase inhibitors (NNRTIs).

OBJECTIVE: To determine whether serum itraconazole concentrations are affected by the type of antiretroviral therapy (NNRTI or protease inhibitor [PI]) being taken concomitantly.

METHODS: This retrospective cohort identified patients on antiretroviral therapy and itraconazole for disseminated histoplasmosis between January 2003 and December 2006 at a large HIV clinic in Houston, TX. Available laboratory values were abstracted from medical records.

RESULTS: Thirteen itraconazole concentrations from 10 patients were available for analysis: 7 patients were on concomitant PIs, 4 on concomitant NNRTIs, and 2 on antiretroviral regimens containing both PIs and NNRTIs. Six of the itraconazole concentrations during concomitant PI treatment were therapeutic (>1.0 µg/mL), in contrast with none in patients taking an NNRTI. All patients taking concomitant NNRTIs had undetectable serum itraconazole concentrations (<0.05 µg/mL). Two patients switched from NNRTI-based to PI-based antiretroviral regimens and subsequently reached therapeutic itraconazole concentrations. Although limited by small sample size, this study provides the largest clinical data among HIV-infected patients demonstrating that coadministration of an NNRTI and itraconazole results in significant decreases in itraconazole blood concentrations, likely by inducing the CYP3A4 enzyme system.

CONCLUSIONS: Itraconazole concentrations should be monitored in patients taking concomitant NNRTIs. PI-based highly active antiretroviral therapy (HAART) may be preferred over NNRTI-based HAART when itraconazole is used to treat HIV-infected patients with disseminated histoplasmosis.

Key Words: AIDS, efavirenz, Histoplasma capsulatum, itraconazole

Published Online, April 28, 2009. www.theannals.com, DOI 10.1345/aph.1L624

This article has been cited by other articles:

				C. Hills-Nieminen, C. A Hughes, S. Houston, and S. D Shafran Drug-Drug Interaction Between Itraconazole and the Protease Inhibitor Lopinavir/Ritonavir Ann. Pharmacother., December 1, 2009; 43(12): 2117 - 2120. [Abstract] [Full Text] [PDF]