title: Effect of Tenofovir Disoproxil Fumarate on Incidence of Chronic Kidney Disease and Rate of Estimated Glomerular Filtration Rate Decrement in HIV-1-Infected Treatment-Naïve Asian Patients: Results from 12-Year Observational Cohort.
abstract: Little evidence is available for the incidence of chronic kidney disease (CKD) and rate of estimated glomerular filtration rate (eGFR) decrement among Asians with low body weight who are susceptible to tenofovir disoproxil fumarate (TDF) nephrotoxicity. In this 12-year observational cohort in Tokyo, we examined 1383 treatment-naïve HIV-1-infected Asians [720 started TDF-containing (TDF group) and 663 started non-TDF-containing (control) combination antiretroviral therapy (cART)]. The CKD incidence was calculated, and the effect of TDF use on CKD development was estimated using logistic regression. The eGFR slopes, before and after cART initiation, were estimated using mixed-effects linear spline models. Most patients were males (median weight, 62.6 kg; 83% started ritonavir-boosted protease inhibitors; median observation duration, 5.08 years). CKD developed in 150 patients (10.8%), with an incidence of 20.6 per 1000 person-years [confidence interval (95% CI), 17.6-24.2]. None developed end-stage renal disease. TDF use was associated with CKD [odds ratio (OR), 1.8; 95% CI, 1.00-3.13; p = 0.052]. The cumulative mean loss in the TDF group, relative to the control, increased over time after 1, 4, and 8 years of TDF exposure (-3.8, -5.5, and -9.0 mL/min/1.73 m2, respectively; p < 0.0001). The eGFR rapidly declined during the first 3 months of cART, particularly in the TDF group (-26.4 vs. -7.4 mL/min/1.73 m2/year in the control). In the TDF group, cART introduction was significantly associated with a faster rate of eGFR decline (from -0.44 to -2.11 mL/min/1.73 m2/year; p = 0.010), whereas in the control, the difference was not significant. For HIV-1-infected Asian patients with low body weight, TDF-containing cART is associated with CKD and faster eGFR declines.
authors.affiliation: 1 AIDS Clinical Center, National Center for Global Health and Medicine , Tokyo, Japan .
authors.forename: Soichiro
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: 1 AIDS Clinical Center, National Center for Global Health and Medicine , Tokyo, Japan .
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishijima
authors.affiliation: 2 Department of Drug Evaluation and Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka , Shizuoka, Japan .
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: 3 Biostatistics Section, Department of Clinical Research and Informatics, Clinical Science Center, National Center for Global Health and Medicine , Tokyo, Japan .
authors.forename: Takuma
authors.initials: T
authors.lastname: Kurosawa
authors.affiliation: 1 AIDS Clinical Center, National Center for Global Health and Medicine , Tokyo, Japan .
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Mutoh
authors.affiliation: 1 AIDS Clinical Center, National Center for Global Health and Medicine , Tokyo, Japan .
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: 1 AIDS Clinical Center, National Center for Global Health and Medicine , Tokyo, Japan .
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.affiliation: 1 AIDS Clinical Center, National Center for Global Health and Medicine , Tokyo, Japan .
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People / Q000706:statistics & numerical data; 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; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D008297:Male; D011480:Protease Inhibitors / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000453:epidemiology / Q000208:ethnology; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use; D014041:Tokyo
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D019438:Ritonavir
keywords: Asian; human immunodeficiency virus-1; low body weight; renal dysfunction; tenofovir disoproxil fumarate; treatment-naïve