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Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific

Tanuma J 1 , Jiamsakul A 2 , Makane A 3 , Avihingsanon A 4 , Ng OT 5 , Kiertiburanakul S 6 Show all authors , Chaiwarith R 7 , Kumarasamy N 8 , Nguyen KV 9 , Pham TT 10 , Lee MP 11 , Ditangco R 12 , Merati TP 13 , Choi JY 14 , Wong WW 15 , Kamarulzaman A 16 , Yunihastuti E 17 , Sim BL 18 , Ratanasuwan W 19 , Kantipong P 20 , Zhang F 21 , Mustafa M 22 , Saphonn V 23 , Pujari S 3 , Sohn AH 24 , TREAT Asia HIV Observational Databases (TAHOD)

Affiliations 

  • 1 AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
  • 2 The Kirby Institute, UNSW Australia, Sydney, Australia
  • 3 Institute of Infectious Diseases, Pune, India
  • 4 The Netherland Australia Thailand Research Collaboration/Thai Red Cross AIDS Research Centre, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  • 5 Department of Infectious Disease and Communicable Disease Centre, Tan Tock Seng Hospital, Singapore, Singapore
  • 6 Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  • 7 Research Institute for Health Sciences, Chiang Mai, Thailand
  • 8 Chennai Antiviral Research and Treatment Clinical Research Site, Y.R. Gaitonde Centre for AIDS Research and Education, Chennai, India
  • 9 National Hospital of Tropical Diseases, Hanoi, Vietnam
  • 10 Infectious Disease Department, Bach Mai Hospital, Hanoi, Vietnam
  • 11 Department of Medicine, Queen Elizabeth Hospital, Hong Kong, China
  • 12 Department of Health, Research Institute for Tropical Medicine, Manila, Philippines
  • 13 Faculty of Medicine, Udayana University & Sanglah Hospital, Bali, Indonesia
  • 14 Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
  • 15 Infectious Diseases and AIDS Unit, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  • 16 Faculty of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia
  • 17 Faculty of Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
  • 18 Department of Medicine, Hospital Sungai Buloh, Sungai Buloh, Malaysia
  • 19 Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • 20 Department of Medicine, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand
  • 21 Beijing Ditan Hospital, Capital Medical University, Beijing, China
  • 22 Medical Department, Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia
  • 23 National Center for HIV/AIDS, Dermatology & STDs, University of Health Sciences, Phnom Penh, Cambodia
  • 24 TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand
PLoS One, 2016;11(8):e0161562.
PMID: 27560968 DOI: 10.1371/journal.pone.0161562

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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