Tenofovir Use is associated with a Reduction in Calculated Glomerular Filtration Rates in the Swiss HIV Cohort Study

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.