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


OPEN ACCESS Citation: Tanuma J, Jiamsakul A, Makane A, Avihingsanon A, Ng OT, Kiertiburanakul S, et al. (2016) Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific. PLoS ONE 11(8): e0161562. doi:10.1371/journal.pone.0161562 Editor: Emmanuel A Burdmann, University of Sao Paulo Medical School, BRAZIL Received: December 3, 2015 Accepted: August 8, 2016 Published: August 25, 2016 Copyright: © 2016 Tanuma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Due to restrictions from the study organizers and ethics committee, the data in TAHOD cannot be made publicly available. External investigator(s) wishing to access the study data can contact the study Project Manager based in Bangkok, Thailand for further information. Boondarika (Tor) Petersen Project Manager, TAHOD TREAT Asia, amfAR – The Foundation for AIDS Research Exchange Tower, 21st Floor, Suite 2104 388 Sukhumvit Road, Klongtoey, Bangkok 10110 Thailand T: +66 (0) 2663 7561 x113 F: +66 (0) 2663 7562 [email protected]

Junko Tanuma1*, Awachana Jiamsakul2, Abhimanyu Makane3, Anchalee Avihingsanon4, Oon Tek Ng5, Sasisopin Kiertiburanakul6, Romanee Chaiwarith7, Nagalingeswaran Kumarasamy8, Kinh Van Nguyen9, Thuy Thanh Pham10, Man Po Lee11, Rossana Ditangco12, Tuti Parwati Merati13, Jun Yong Choi14, Wing Wai Wong15, Adeeba Kamarulzaman16, Evy Yunihastuti17, Benedict LH Sim18, Winai Ratanasuwan19, Pacharee Kantipong20, Fujie Zhang21, Mahiran Mustafa22, Vonthanak Saphonn23, Sanjay Pujari24, Annette H. Sohn25, TREAT Asia HIV Observational Databases (TAHOD)¶ 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 Institute of Infectious Diseases, Pune, India, 25 TREAT Asia, amfAR – The Foundation for AIDS Research, Bangkok, Thailand ¶ Membership of the TREAT Asia HIV Observational Databases (TAHOD) can be found in the Acknowledgments. * [email protected]

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

PLOS ONE | DOI:10.1371/journal.pone.0161562 August 25, 2016

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Renal Function during TDF Use in the Asia-Pacific

Funding: This work was supported through the U.S. National Institutes of Health’s National Institute of Allergy and Infectious Diseases Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Cancer Institute, as part of the International Epidemiologic Databases to Evaluate AIDS (IeDEA; U01AI069907, http://www., and the Dutch Ministry of Foreign Affairs through a partnership with Stichting Aids Fonds. Queen Elizabeth Hospital and the Integrated Treatment Centre received additional support from the Hong Kong Council for AIDS Trust Fund. TREAT Asia (Therapeutics Research Education and AIDS Training - Foundation for AIDS Research) is also supported by ViiV Healthcare (https://www. The Kirby Institute is funded by the Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, UNSW Australia. The content of this analysis is solely the responsibility of the authors and does not necessarily represent the official views of any of the governments or institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.

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 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 50 vs. 30, hazard ratio [HR] 5.39, 95%CI 2.52–11.50, p 140 mmHg or diastolic >90 mmHg measurement. Trends in crude rates of S-Cr testing for each year on TDF were also explored using Poisson regression with follow-up time beginning from TDF initiation.

Analysis (ii): To determine factors associated with time to renal dysfunction on TDF Patient selection followed the same criteria as per analysis (i). TDF-related renal toxicity was defined as having eGFR reduction of at least 30% of the baseline value and

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

In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for...
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