Differences in Calculated Glomerular Filtration Rates in Efavirenz- or Tenofovir-treated Adults in ESS40006
Melanie Thompson*1, R Haubrich2, D Margolis3, S Schneider4, R Schooley2, K Pappa5, J Sail5, L Yau5, and J Hernandez5
1AIDS Res Consortium of Atlanta, GA, US; 2Univ of California, San Diego, US; 3Univ of North Carolina at Chapel Hill, US; 4St Mary Med Ctr Care Clin, Long Beach, CA, US; and 5GlaxoSmithKline, Research Triangle Park, NC, US
observational cohorts have reported a higher degree of decline in calculated glomerular filtration rates (GFR) in patients treated with tenofovir (TDF), particularly in combination with boosted protease
inhibitors (PI), compared with nucleosides.
Methods: ESS40006 was
primarily designed to compare 2 regimens of aprenavir/ritonavir
(APV/r) (600/100 vs 900/100 twice daily) in subjects
failing their current ART regimen. In addition, non-nucleoside reverse
transcriptase inhibitor (NNRTI)-naïve subjects were assigned to receive efavirenz (EFV), abacavir (ABC), and
1 additional NRTI, while NNRTI-experienced subjects were assigned to receive
TDF in place of EFV. Descriptive statistics were summarized for subjects
treated with EFV or TDF. The modification of diet in renal disease (MDRD) formula
was used to calculate GFR. Potential predictors of GFR decline over 48 weeks of
therapy, including baseline demographic data, CDC HIV-1 classification, CD4+
cell count, plasma HIV-1 RNA, prior therapy, concurrent ART, weight, and
clinical laboratory results were assessed using multiple regression analyses.
Results: The median
calculated GFR at baseline was comparable between the 2 groups (EFV-treated
subjects [n = 38], 107.36;
TDF-treated subjects [n = 76],
108.24). However, there were statistically significant differences in the
median change in calculated GFR between the EFV-treated and TDF-treated
subjects (median change from baseline at 24 weeks was 12.66 vs
–9.85 [p <0.001] and at 48 weeks: –0.37
vs –11.07 [p
= 0.004]). In the TDF group, the median reduction in calculated GFR from baseline
was also statistically significant at both weeks 24 (p <0.001) and 48 (p <0.001).
The only predictor of a decline in GFR in the multivariable model after
adjusting for baseline GFR was TDF use.
Conclusions: For NNRTI-experienced
subjects treated with TDF in this study, a significant decline in the median
calculated GFR was observed over 48 weeks of therapy. This decline was not seen
in the NNRTI-naive subjects treated with EFV in the same study. TDF use was the
only predictor of GFR decline using multiple regression analysis. The clinical
significance of these changes in calculated GFR deserves further study.