title: Elevated plasma concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors in patients coinfected with human immunodeficiency virus and hepatitis B or C: case series and literature review.
abstract: OBJECTIVE
  To evaluate antiretroviral pharmacokinetics in patients who are coinfected with human immunodeficiency virus (HIV) and hepatitis B and/or C virus. Specifically, we sought to determine whether coinfection results in higher than expected concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs).
  
  
  METHODS
  Case series.
  
  
  METHODS
  Human immunodeficiency virus clinic.
  
  
  METHODS
  Twenty-six patients infected with HIV and hepatitis B and/or C virus.
  
  
  RESULTS
  Patients' plasma trough concentrations (Cmeasured) of protease inhibitors and NNRTIs were compared with population average trough concentrations reported in the literature (Cpredicted). Trough concentrations were obtained irrespective of the patients' liver function. A concentration ratio of Cmeasured: Cpredicted was determined for each patient. The mean concentration ratio of the 26 patients was 1.43 (95% confidence interval 1.08-1.78). For the six patients taking nelfinavir, the ratio of nelfinavir's active metabolite (M8): parent drug was calculated. The median M8:nelfinavir ratio for these six patients was 69% lower than what has been reported in a general HIV population.
  
  
  CONCLUSIONS
  These preliminary findings suggest that trough concentrations of protease inhibitors and NNRTIs may be elevated in patients with HIV infection who are coinfected with hepatitis B and/or C, compared with a general population of patients with HIV infection. Until further investigation defines the relationship between coinfection, metabolic dysfunction, and increased antiretroviral exposure, therapeutic drug monitoring may be helpful to identify coinfected patients at risk for antiretroviral toxicity secondary to elevated plasma drug concentrations.
authors.affiliation: Clinical Pharmacokinetics Research Laboratory, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. robertsonsa@cc.nih.gov
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Robertson
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Scarsi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Postelnick
authors.forename: Patrick
authors.initials: P
authors.lastname: Lynch
mesh_terms: D002851:Chromatography, High Pressure Liquid; D015658:HIV Infections / Q000150:complications* / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006207:Half-Life; D006509:Hepatitis B / Q000150:complications* / Q000378:metabolism*; D006526:Hepatitis C / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology; D008111:Liver Function Tests; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase