title: Increase in serum mitochondrial creatine kinase levels induced by tenofovir administration.
abstract: Recently, 2 monoclonal antibodies that specifically inhibit mitochondrial creatine kinase (MtCK) activity have been developed. In this study, we measured the serum MtCK activity in HIV-1-infected individuals (n = 100) by employing a novel method using these antibodies. The mean serum MtCK activity in 44 patients treated with highly active antiretroviral therapy (HAART) including tenofovir disoproxil fumarate (TDF) was 16.0 IU/L. The MtCK activity was significantly higher in patients receiving TDF than in those receiving HAART without TDF (3.4 IU/L) or in naïve patients (6.9 IU/L) (Tukey-Kramer test, p < 0.0001 and p = 0.0029, respectively). The serum MtCK activity reached a plateau at 1 month after the initiation of TDF administration and decreased upon discontinuation. It showed no significant correlation with the trough plasma TDF concentration, serum creatinine level, or red blood cell count. The activity was elevated in 75% of the patients receiving TDF, and this elevation was specific to TDF; it was not observed with other anti-HIV drugs. In addition, our report emphasizes the careful interpretation of creatine kinase-MB (CK-MB) test results in patients receiving TDF because MtCK in serum could cause false-positive results on a conventional CK-MB test, which does not include MtCK-specific inhibitory antibodies.
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, Osaka, 540-0006, Japan. dai@onh.go.jp
authors.forename: Dai
authors.initials: D
authors.lastname: Watanabe
authors.forename: Munehiro
authors.initials: M
authors.lastname: Yoshino
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yagura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirota
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yonemoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Bando
authors.forename: Keishiro
authors.initials: K
authors.lastname: Yajima
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Koizumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Otera
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Tominari
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuwahara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Uehira
authors.forename: Takuma
authors.initials: T
authors.lastname: Shirasaka
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000737:chemistry; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D052281:Creatine Kinase, Mitochondrial Form / Q000097:blood*; D004587:Electrophoresis, Agar Gel / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D063065:Organophosphonates; D000068698:Tenofovir; D052281:Creatine Kinase, Mitochondrial Form; D000225:Adenine