Misleading results of screening for illicit drugs during efavirenz treatment

• Published in: AIDS (London) Vol. 21; no. 10; pp. 1390 - 1391
• Main Authors: RÖDER, Claudia Stephanie, HEINRICH, Tilman, GEHRIG, Anne-Kathrin, MIKUS, Gerd
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 19.06.2007
• Subjects: AIDS/HIV; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Benzodiazepines - analysis; Benzoxazines - administration & dosage; Biological and medical sciences; Dronabinol - analysis; Drug Administration Schedule; Human viral diseases; Humans; Immunoassay - methods; Infectious diseases; Medical sciences; Midazolam - pharmacokinetics; Pharmacology. Drug treatments; Reverse Transcriptase Inhibitors - administration & dosage; Substance Abuse Detection - methods; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Antiretroviral agent; Benzoxazine derivatives; RNA-directed DNA polymerase; Acetylenic compound; Enzyme; Illicit drug; Non nucleoside compound; Transferases; Enzyme inhibitor; Medical screening; Efavirenz; Allosteric inhibitor; Nucleotidyltransferases; Treatment; Reverse transcriptase inhibitor; Antiviral
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e32814e6b3e

We investigated in 12 healthy subjects the influence of efavirenz, a non-nucleoside reverse transcriptase inhibitor, on the pharmacokinetics of midazolam, which served as a marker for CYP3A4 activity. The study was authorized by the Ethics Committee of the Medical Faculty (University of Heidelberg, Germany) as well as the Competent Regulatory Authority. All study participants gave their written informed consent. They received 3mg midazolam by mouth together with the first dose of efavirenz. Thereafter, efavirenz was administered in a daily dose of 400 mg by mouth for 14 days. On day 8, a safety check including a routine screening for illicit drugs was performed, in which 11 out of 12 subjects screened positive for benzodiazepines and eight for tetrahydrocannabinol using the Triage 8 (Biosite, San Diego, California, USA) single-use, rapid immunochemical assay. In the product information of efavirenz an interference of efavirenz with the CEDIA-DAU multi-level tetrahydrocannabinol assay is mentioned. Earlier reports characterized the interference by efavirenz in an estradiol enzyme-linked immunosorbent assay and with several tetrahydrocannabinol immunoassays. We therefore suspected that efavirenz or its metabolites may also cause false-positive results for benzodiazepines through crossreactivity.