학술논문
Tenofovir Use is associated with a Reduction in Calculated Glomerular Filtration Rates in the Swiss HIV Cohort Study
Document Type
Article
Author
Fux, Christoph A; Simcock, Mathew; Wolbers, Marcel; Bucher, Heiner C; Hirschel, Bernard; Opravil, Milos; Vernazza, Pietro; Cavassini, Matthias; Bernasconi, Enos; Elzi, Luigia; Furrer, Hansjakob; Battegay, M; Bernasconi, E; Böni, J; Bucher, H; Bürgisser, Ph; Cattacin, S; Cavassini, M; Dubs, R; Egger, M; Elzi, L; Erb, P; Fischer, M; Flepp, M; Fontana, A; Francioli, P; Furrer, H; Fux, C; Gorgievski, M; Günthard, H; Hirschel, B; Hösli, I; Kahlert, Ch; Kaiser, L; Karrer, U; Keiser, O; Kind, C; Klimkait, Th; Ledergerber, B; Martinez, B; Müller, N; Nadal, D; Opravil, M; Paccaud, F; Pantaleo, G; Perrin, L; Piffaretti, J-C; Rauch, A; Rickenbach, M; Rudin, C; Schmid, P; Schultze, D; Schüpbach, J; Speck, R; Taffé, P; Tarr, P; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S
Source
Antiviral Therapy; November 2007, Vol. 12 Issue: 8 p1165-1174, 10p
Subject
Language
ISSN
13596535
Abstract
Background A growing number of case reports have described tenofovir (TDF)-related proximal renal tubulopathy and impaired calculated glomerular filtration rates (cGFR). We assessed TDF-associated changes in cGFR in a large observational HIV cohort.Methods We compared treatment-naive patients or patients with treatment interruptions =12 months starting either a TDF-based combination antiretroviral therapy (cART) (n=363) or a TDF-sparing regime (n=715). The predefined primary endpoint was the time to a 10 ml/min reduction in cGFR, based on the Cockcroft-Gault equation, confirmed by a follow-up measurement at least 1 month later. In sensitivity analyses, secondary endpoints including calculations based on the modified diet in renal disease (MDRD) formula were considered. Endpoints were modelled using pre-specified covariates in a multiple Cox proportional hazards model.Results Two-year event-free probabilities were 0.65 (95% confidence interval [CI] 0.58–0.72) and 0.80 (95% CI 0.76–0.83) for patients starting TDF-containing or TDF-sparing cART, respectively. In the multiple Cox model, diabetes mellitus (hazard ratio [HR]=2.34 [95% CI 1.24–4.42]), higher baseline cGFR (HR=1.03 [95% CI 1.02–1.04] by 10 ml/min), TDF use (HR=1.84 [95% CI 1.35–2.51]) and boosted protease inhibitor use (HR=1.71 [95% CI 1.30–2.24]) significantly increased the risk for reaching the primary endpoint. Sensitivity analyses showed high consistency.Conclusion There is consistent evidence for a significant reduction in cGFR associated with TDF use in HIV-infected patients. Our findings call for a strict monitoring of renal function in long-term TDF users with tests that distinguish between glomerular dysfunction and proximal renal tubulopathy, a known adverse effect of TDF.