title: No observable correlation between central nervous system side effects and EFV plasma concentrations in Japanese HIV type 1-infected patients treated with EFV containing HAART.
abstract: The present study assessed the relationship between central nervous system (CNS) side effects and plasma concentrations of efavirenz (EFV) in Japanese HIV-1-infected patients. Subjects consisted of 69 HIV-1-infected patients (57 therapy-naive and 12 therapy-experienced patients) being treated using EFV in combination with other antiretroviral agents at the outpatient HIV clinic. Successful virological treatment was achieved in 61 patients. Eight patients discontinued EFV containing therapy because CNS symptoms did not resolve (four patients), EFV-specific mutations were detected (two patients), or skin rash was observed (two patients). Mean EFV plasma concentration for 61 effectively treated patients, measured at 15 h postdosing, was 2.42 microg/ml (range: 0.78-6.82 microg/ml). This EFV concentration range contributed to suppressed viral load in these Japanese patients. Adverse CNS effects were observed in 19 patients soon after therapy onset. These effects disappeared within 1 month except for four patients who suffered severe CNS side effects. Mean EFV plasma concentrations were not significantly different between subjects with (2.45 +/- 1.08 microg/ml) and without (2.42 +/- 1.40 microg/ml) CNS side effects. We concluded no correlation existed between the plasma EFV concentration and the emergence of CNS side effects in Japanese HIV-1-infected patients. Further investigations, enforced with the drug concentration measurement at earlier time points and more appropriate assessment of CNS symptoms, are required.
authors.affiliation: Department of Pharmacy, National Hospital Organization Nagoya Medical Center (Tokai Area Central Hospital for AIDS Treatment and Research), Nagoya,Aichi, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Ibe
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kudaka
authors.forename: Naoya
authors.initials: N
authors.lastname: Okumura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirano
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Suzuki
authors.forename: Naoto
authors.initials: N
authors.lastname: Mamiya
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hamaguchi
authors.forename: Tsuguhiro
authors.initials: T
authors.lastname: Kaneda
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002490:Central Nervous System / Q000187:drug effects*; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz