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
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 18:19
Last modification date
20/08/2019 13:55