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

• Published in: Antiviral therapy 2007-01, Vol.12 (8), p.1165-1173
• Main Authors: FUX, Christoph A, SIMCOCK, Mathew, FURRER, Hansiakob, WOLBERS, Marcel, BUCHER, Heiner C, HIRSCHEL, Bernard, OPRAVIL, Milos, VERNAZZA, Pietro, CAVASSINI, Matthias, BERNASCONI, Enos, ELZI, Luigia
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Adenine - therapeutic use; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active; Antiviral agents; Biological and medical sciences; Cohort Studies; Female; Glomerular Filtration Rate - drug effects; HIV Infections - drug therapy; HIV-1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Kidney - drug effects; Kidney - physiopathology; Male; Medical sciences; Organophosphonates - pharmacology; Organophosphonates - therapeutic use; Pharmacology. Drug treatments; Switzerland; Tenofovir; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350701200812

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. 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. 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. 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.