title: Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific.
abstract: BACKGROUND
  In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use.
  
  
  METHODS
  We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.
  
  
  RESULTS
  Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018).
  
  
  CONCLUSIONS
  Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.
authors: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors: Junko
authors: J
authors: Tanuma
authors: The Kirby Institute, UNSW Australia, Sydney, Australia.
authors: Awachana
authors: A
authors: Jiamsakul
authors: Institute of Infectious Diseases, Pune, India.
authors: Abhimanyu
authors: A
authors: Makane
authors: The Netherland Australia Thailand Research Collaboration/Thai Red Cross AIDS Research Centre, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors: Anchalee
authors: A
authors: Avihingsanon
authors: Department of Infectious Disease and Communicable Disease Centre, Tan Tock Seng Hospital, Singapore, Singapore.
authors: Oon Tek
authors: OT
authors: Ng
authors: Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors: Sasisopin
authors: S
authors: Kiertiburanakul
authors: Research Institute for Health Sciences, Chiang Mai, Thailand.
authors: Romanee
authors: R
authors: Chaiwarith
authors: Chennai Antiviral Research and Treatment Clinical Research Site, Y.R. Gaitonde Centre for AIDS Research and Education, Chennai, India.
authors: Nagalingeswaran
authors: N
authors: Kumarasamy
authors: National Hospital of Tropical Diseases, Hanoi, Vietnam.
authors: Kinh Van
authors: KV
authors: Nguyen
authors: Infectious Disease Department, Bach Mai Hospital, Hanoi, Vietnam.
authors: Thuy Thanh
authors: TT
authors: Pham
authors: Department of Medicine, Queen Elizabeth Hospital, Hong Kong, China.
authors: Man Po
authors: MP
authors: Lee
authors: Department of Health, Research Institute for Tropical Medicine, Manila, Philippines.
authors: Rossana
authors: R
authors: Ditangco
authors: Faculty of Medicine, Udayana University & Sanglah Hospital, Bali, Indonesia.
authors: Tuti Parwati
authors: TP
authors: Merati
authors: Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors: Jun Yong
authors: JY
authors: Choi
authors: Infectious Diseases and AIDS Unit, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Wing Wai
authors: WW
authors: Wong
authors: Faculty of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors: Adeeba
authors: A
authors: Kamarulzaman
authors: Faculty of Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
authors: Evy
authors: E
authors: Yunihastuti
authors: Department of Medicine, Hospital Sungai Buloh, Sungai Buloh, Malaysia.
authors: Benedict Lh
authors: BL
authors: Sim
authors: Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors: Winai
authors: W
authors: Ratanasuwan
authors: Department of Medicine, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand.
authors: Pacharee
authors: P
authors: Kantipong
authors: Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors: Fujie
authors: F
authors: Zhang
authors: Medical Department, Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia.
authors: Mahiran
authors: M
authors: Mustafa
authors: National Center for HIV/AIDS, Dermatology & STDs, University of Health Sciences, Phnom Penh, Cambodia.
authors: Vonthanak
authors: V
authors: Saphonn
authors: Institute of Infectious Diseases, Pune, India.
authors: Sanjay
authors: S
authors: Pujari
authors: TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand.
authors: Annette H
authors: AH
authors: Sohn
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D016208:Databases, Factual; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D016012:Poisson Distribution; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir; D003404:Creatinine