Renal dysfunction with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy regimens is not observed more frequently - A cohort and case-control study

Background: Tenofovir disoproxil fumarate (tenofovir DF), the first nucleotide analogue reverse transcriptase inhibitor approved for the treatment of HIV infection, has been associated with renal dysfunction in isolated cases. We investigated the overall incidence and risk of renal dysfunction in individuals receiving tenofovir DF and compared this with other antiretrovirals. Methods: Data from the Chelsea and Westminster cohort were analyzed to reveal HIV-positive individuals with a creatinine value greater than 120 mumol/L at any time, the upper limit of normal used by our reference laboratory. These individuals were classified according to antiretroviral exposure and time exposed. A matched case-control study was performed comparing patients who had received tenofovir DF and subsequently developed a creatinine value greater than 120 mumol/L against controls who had been treated with tenofovir DF and had not experienced a creatinine elevation. Results: Of 4183 HIV-positive patients, 1175 were identified as having a recorded creatinine value >120 mumol/L. Comparison of antiretroviral-naive patients and patients exposed to tenofovir DF- and non-tenofovir DF-containing regimens revealed a lower rate ratio and probability of developing a creatinine value >120 mumol/L in patients exposed to tenofovir DF (rate ratio vs. no antiretrovirals = 0.22, 95% confidence interval [CI]: 0.07-0.69; P < 0.001) with no significant difference between HAART regimens, corrected for duration of exposure. Of the 1058 individuals who were exposed to tenofovir DF, 84 (8%) patients experienced a creatinine value >120 mumol/L subsequent to exposure. An alternative etiology of renal dysfunction was found in 75 (90%) of these individuals. Conclusions: Tenofovir DF is not associated with renal dysfunction more frequently than other antiretroviral drugs, and the occurrence of renal dysfunction in this context is usually attributable to other causes.