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.
Bibliographical noteFunding Information:
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. iedea.org/), 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. viivhealthcare.com/community-partnerships/projecttours/amfar-treat-asia/introduction.aspx). 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.
© 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.
All Science Journal Classification (ASJC) codes