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Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study

Fux, C. A.
Simcock, Mathew
Wolbers, Marcel
Bucher, H. C.
Opravil, Milos
Vernazza, Pietro
Cavassini, Matthias
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Published in Antiviral Therapy. 2007, vol. 12, no. 8, p. 1165-1173
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 > or = 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.
Keywords Adenine/ analogs & derivatives/pharmacology/therapeutic useAnti-HIV Agents/ pharmacology/therapeutic useAntiretroviral Therapy, Highly ActiveCohort StudiesFemaleGlomerular Filtration Rate/ drug effectsHIV Infections/ drug therapyHiv-1HumansKidney/ drug effects/physiopathologyMalePhosphonic Acids/ pharmacology/therapeutic useSwitzerland
PMID: 18240857
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FUX, C. A. et al. Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study. In: Antiviral Therapy, 2007, vol. 12, n° 8, p. 1165-1173. https://archive-ouverte.unige.ch/unige:7244

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Deposited on : 2010-06-21

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