title: Successful use of reduced-dose efavirenz in a patient with human immunodeficiency virus infection: case report and review of the literature.
abstract: Efavirenz, a nonnucleoside reverse transcriptase inhibitor, is a highly effective and widely prescribed antiretroviral agent. It is recommended as first-line treatment of human immunodeficiency virus (HIV) infection. The standard dose of efavirenz is 600 mg/day; however, adverse central nervous system effects limit its use. Few data citing use of efavirenz at lower doses have been published. We describe a 35-year-old man with HIV infection whose virologic suppression was maintained after 18 months of treatment with efavirenz 400 mg/day. Genetic testing for cytochrome P450 (CYP) 2B6 showed that the patient was a heterozygous variant; patients with this polymorphism tend to have higher plasma efavirenz concentrations and slower plasma efavirenz clearance (prolonged elimination half-lives). Therapeutic drug monitoring also supported the dose reduction in this patient. Even with the 400-mg dose, the patient's plasma trough concentrations exceeded the upper limit of the therapeutic range. However, as he remained completely asymptomatic with this dose, no further dose reduction was necessary. This case report provides evidence that reduced efavirenz doses may be effective in the treatment of HIV infection. In addition, this case demonstrates that pharmacogenetic and pharmacokinetic testing combined with therapeutic drug monitoring may be used to guide reduced-dose, efavirenz-based therapy.
authors.affiliation: Department of Health and Human Services, Long Beach, California 90815, USA. Mauro_Torno@longbeach.gov
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Torno
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Witt
authors.forename: Akihiko
authors.initials: A
authors.lastname: Saitoh
authors.forename: Courtney V
authors.initials: CV
authors.lastname: Fletcher
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D048588:Benzoxazines / Q000627:therapeutic use*; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D016903:Drug Monitoring; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D011110:Polymorphism, Genetic
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz