Minor changes in calculated creatinine clearance and anion-gap are associated with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy.
BACKGROUND
Tenofovir 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 TDF- and non-TDF-containing highly active antiretroviral therapy (HAART).


METHODS
All 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.


RESULTS
Of 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-6.80 (standard error 2.2); P = 0.005 and P = 0.032, respectively] after adjusting for baseline anion-gap and CCrCl, respectively. Two cases of TDF-associated renal failure were observed.


CONCLUSIONS
Overt 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.
Winston
A
A
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia. alan_winston71@yahoo.co.uk
Amin
J
J
Mallon
Pwg
P
Marriott
D
D
Carr
A
A
Cooper
D A
DA
Emery
S
S
D000136:Acid-Base Equilibrium / Q000187:drug effects*; D058186:Acute Kidney Injury / Q000139:chemically induced; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D015497:HIV-1; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine