title: Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight: results from 10 years of follow-up.
abstract: OBJECTIVE
  To investigate the effect of long-term tenofovir disoproxil fumarate (TDF) use on renal function, especially in patients with low body weight who are vulnerable to TDF nephrotoxicity.
  
  
  METHODS
  A single-center, observational study in Tokyo, Japan.
  
  
  METHODS
  We performed a 10 years cohort study of 792 HIV-1-infected patients. The effect of long-term TDF use on estimated glomerular filtration rate (eGFR) was investigated on treatment-naive patients who started TDF-containing antiretroviral therapy (n = 422) and those who started abacavir-containing antiretroviral therapy as control (n = 370). Three renal endpoints were examined by the logistic regression model: decrement in eGFR of higher than 10 ml/min per 1.73 m relative to the baseline, more than 25% decrement in eGFR, and eGFR lower than 60 ml/min per 1.73 m at least 3 months apart. The loss in eGFR was estimated using linear mixed models for repeated measures.
  
  
  RESULTS
  The median weight at baseline was 63 kg. TDF use increased the risk of all three renal outcomes compared with the control group: higher than 10 ml/min per 1.73 m decrement in eGFR [adjusted odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.45-3.14, P < 0.001], more than 25% decrement (adjusted OR = 2.1, 95% CI 1.50-2.90, P < 0.001), and eGFR lower than 60 ml/min per 1.73 m at least 3 months apart (adjusted OR = 3.9, 95% CI 1.62-9.36, P = 0.002). The cumulative mean loss relative to the control after 1, 2, 3, 4, and 5 years of TDF exposure was -3.8, -3.6, -5.5, -6.6, and -10.3 ml/min per 1.73 m, respectively, indicating that the loss in eGFR increased over time (P < 0.001).
  
  
  CONCLUSIONS
  In this cohort of patients with low body weight, TDF exposure increased the risk of renal dysfunction. Furthermore, the loss in eGFR relative to the control increased continuously up to 5 years.
authors.affiliation: aAIDS Clinical Center, National Center for Global Health and Medicine, Tokyo bCenter for AIDS Research, Kumamoto University, Kumamoto cBiostatistics Section, Department of Clinical Research and Informatics, Clinical Science Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishijima
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mizushima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Aoki
authors.forename: Koji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Ei
authors.initials: E
authors.lastname: Kinai
authors.forename: Haruhito
authors.initials: H
authors.lastname: Honda
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yazaki
authors.forename: Junko
authors.initials: J
authors.lastname: Tanuma
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Tsukada
authors.forename: Katsuji
authors.initials: K
authors.lastname: Teruya
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001835:Body Weight; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000139:chemically induced*; D000068698:Tenofovir; D014041:Tokyo
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine