BackgroundTenofovir disoproxil fumarate (Tenofovir DF, TDF), the first nucleotide reverse transcriptase inhibitor approved for the treatment of HIV disease, has been associated with renal dysfunction in isolated cases. The aim of this study was to assess changes in renal parameters in individuals receiving TDFand non-TDF-containing highly active antiretroviral therapy (HAART). MethodsAll individuals on HAART attending our clinic were included in the analysis. Time-weighted changes in serum creatinine, calculated creatinine clearance (CCrCl) and anion-gap were assessed for individuals on TDF-and non-TDF HAART. ResultsOf 948 individuals on HAART, 290 (31%) and 618 (65%) were on TDF-and non-TDF HAART, with 40 (4%) having ceased TDF HAART. Baseline values for serum creatinine, CCrCl and anion-gap were similar for those on TDF-and non-TDF HAART. In a multivariate analysis, statistically significant differences were observed in time-weighted change from baseline in anion-gap and CCrCl between individuals on TDF-and non-TDF HAART [mean difference in change between groups: anion-gap 0.78 mmol/L (standard error, 0.19) and CCrCl À 6.80 (standard error 2.2); P 5 0.005 and P 5 0.032, respectively] after adjusting for baseline anion-gap and CCrCl, respectively. Two cases of TDF-associated renal failure were observed. ConclusionOvert renal failure with TDF HAART is rare. However, subtle but statistically significant changes in anion-gap and CCrCl were observed which were associated with TDF HAART. These parameters may be of use in monitoring individuals on HAART. Cidofovir and adefovir, compounds structurally related to TDF, have been associated with an increased risk of acute renal insufficiency. In particular, a dose-and timedependent development of a Fanconi-like syndrome has been reported [5,6]. In pivotal studies assessing the safety and efficacy of TDF, renal safety profiles were found to be similar in individuals receiving and in those not receiving TDF-containing highly active antiretroviral therapy (HAART) [2][3][4]. In addition, a recent large cohort has described no significant evidence of renal dysfunction with the use of TDF in clinical practice [7]. However, there are mounting numbers of anecdotal reports describing Fanconi's syndrome and renal insufficiency induced by TDF therapy [8][9][10][11][12][13][14][15][16][17][18]. Predisposing factors for the development of acute renal failure with the use of TDF remain obscure.Several groups reporting no significant evidence of renal dysfunction with the use of TDF have relied on serum creatinine as a marker of renal function [7]. A recent report utilizing glomerular filtration rate (GFR) calculated on the basis of a 24-h urine collection has observed a lower GFR associated with TDF treatment [19].The aim of this study was to investigate changes in anion-gap and calculated creatinine clearance (CCrCl) in a large cohort of HIV-1-infected individuals receiving TDFand non-TDF-containing HAART. Methods Study designAll individuals currently on HAART attending the Departmen...

ART initiation resulted in reductions in levels of CVD-associated biomarkers; however, although they improved, markers of endothelial dysfunction and monocyte activation remained elevated. How these persistent abnormalities affect CVD risk in HIV infection remains to be determined.