title: Clinical evidence of interaction between itraconazole and nonnucleoside reverse transcriptase inhibitors in HIV-infected patients with disseminated histoplasmosis.
abstract: 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 microg/mL), in contrast with none in patients taking an NNRTI. All patients taking concomitant NNRTIs had undetectable serum itraconazole concentrations (<0.05 microg/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.
authors.affiliation: Section of Infectious Diseases, Baylor College of Medicine, Houston, TX 77009, USA. randrade@bcm.tmc.edu
authors.forename: Roberto A
authors.initials: RA
authors.lastname: Andrade
authors.forename: Richard T
authors.initials: RT
authors.lastname: Evans
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hamill
authors.forename: Teddy
authors.initials: T
authors.lastname: Zerai
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Giordano
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006660:Histoplasmosis / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000008:administration & dosage*; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D017964:Itraconazole; D054303:HIV Reverse Transcriptase