Background:  Tenofovir DF (TDF) is the first nucleotide analog reverse transcriptase inhibitor (NRTI) approved for treatment of HIV disease. TDF is renally excreted via a combination of glomerular filtration and active tubular secretion. Renal impairment (including acute renal failure and Fanconi syndrome) has been reported in association with TDF use. Although the majority of cases have been associated with underlying systemic or renal disease, some cases occurred in patients without any identified risk factor.

Methods:  To determine the effect of TDF vs NRTI on creatinine clearance we conducted a prospective longitudinal study of 476 HIV-infected patients treated with HAART by the Johns Hopkins AIDS service with up to 1 year follow-up. 211 took TDF and 265 used an NRTI, both starting in 2001. We assessed change in calculated creatinine clearance (Cockcroft-Gault equation) at start of treatment compared to that at the end of the observation period.  Statistical comparisons were performed using paired t-test (before-after), independent t-test (TDF vs NRTI), and multivariate general linear modeling to assess multiple risk factors for creatinine clearanceL change.

Results:  Median duration of follow-up was 204 days for TDF users and 289 days for NRTI users (p < 0.05). Median serum creatinine at start of treatment was 0.8 and 0.8 mg/dL for the TDF and NRTI groups, respectively, with a significant mean change over time of +0.1 and +0.1 (both p <0.05).  Median creatinine clearance change was -15.2 and -12.8 (both p <0.01), and median percentage of creatinine clearance decline was 12.5% and 11.1% (both p <0.01).  Factors associated with percentage creatinine clearance decline were higher HIV RNA (p = 0.03) and lower CD4 (p = 0.03) at start of treatment, diabetes (p=.04), and hypertension (p = 0.009).  Adjusting for these variables in a multivariate analysis of creatinine clearance decline, TDF use, concurrent use of ddI with TDF, prior use of adefovir, age, sex, and injection drug use were not significant predictors of creatinine clearance decline.

Conclusions:  Significant declines in creatinine clearance were seen in all HIV-infected patients studied, with no significant difference seen between groups. The use of TDF was not a significant predictor of creatinine clearance decline. Further studies are needed to evaluate disease state and the concurrent use of nephrotoxic agents as predictors of creatinine clearance decline in this population.

Keywords: Tenofovir; Nephrotoxicity; Antiretroviral therapy