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

Details

Serval ID
serval:BIB_1FF1C058E28E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study.
Journal
Antiviral Therapy
Author(s)
Fux C.A., Simcock M., Wolbers M., Bucher H.C., Hirschel B., Opravil M., Vernazza P., Cavassini M., Bernasconi E., Elzi L., Furrer H.
ISSN
1359-6535
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
12
Number
8
Pages
1165-1173
Language
english
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, Adenine/pharmacology, Anti-HIV Agents/pharmacology, Anti-HIV Agents/therapeutic use, Antiretroviral Therapy, Highly Active, Cohort Studies, Female, Glomerular Filtration Rate/drug effects, HIV Infections/drug therapy, HIV-1, Humans, Kidney/drug effects, Kidney/physiopathology, Male, Phosphonic Acids/pharmacology, Phosphonic Acids/therapeutic use, Switzerland
Pubmed
Web of science
Create date
24/09/2009 17:19
Last modification date
20/08/2019 12:55
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