Impact of emtricitabine/tenofovir (FTC/TDF) on renal function in antiretroviral‐naïve patients≥50 years ‐ TRIP study
Authors: Blanco J , Castaño M , Olalla J , Domingo P , Arazo P , Gómez‐Sirvent J , Riera M , Pulido F , Vera F , Vergara A , Aguirrebengoa K , Portilla J , Pedrol E 
Published: November 2012

PurposeIn the last decade the prevalence of HIV‐infected patients≥50 years of age has increased. FTC/TDF is nowadays one of the cornerstones of cART in naïve patients, generally considered safe and well tolerated; nevertheless there is a continuous debate about the renal safety of TDF, due to the report of cases linking this treatment with renal failure and tubular dysfunction. In addition, there is a well‐recognized age‐related decline in renal function. Our aim was to describe the impact of cART regimen (FTC/TDF vs. others) on renal function of subjects who start cART at≥50 years old.MethodsNational, retrospective cohort analysis of HIV‐infected patients>50 y at the time they began the first cART (Jan 1, 2006 – Dec 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF versus other NRTI regimens (no TDF). For this analysis we excluded subjects taking potentially nephrotoxic drugs at baseline. We compared the impact of FTC/TDF vs. no‐TDF regimens (main groups) on renal function by means of the changes, during the first 12 months of treatment, in glomerular filtration rate estimated by the CKD‐EPI formula, and by the analysis of time to renal deterioration during the complete follow up (defined as progression to an EPI‐CKD value<60 mL/min/1.73 m2 in subjects with baseline values>60). We also compared these outcomes among FTC/TDF users, according to the third agent: PI vs. NNRTI, and lopinavir/r vs. efavirenz.ResultsWe included 125 patients, median age: 54.8 y, 82% males, median CD4 count 235 cells/µl, median viral load 4.7 log, follow up: median 19 months, max: 66 months. Of them, 82 started with FTC/TDF and 43 with other NRTIs (no TDF). During the follow‐up 13/125 patients taking FTC/TDF (11%) presented with renal deterioration. The Cox regression model including age, sex, transmission category, baseline CD4 count and viral load, FTC/TDF use, PI/NNRTI use, and LPVr/EFV use showed a hazard ratio for renal deterioration of 4.13 (95% CI 0.92, 18.5) for LPV/r users. The table shows the evolution of glomerular filtration rate, and proportion and risk of renal deterioration.ConclusionIn subjects starting cART after 50 years of age, we have not found significant changes in glomerular filtration rate associated with the use of FTC/TDF‐based regimens. Overall, the risk of renal deterioration was 4.1 times higher for LPV/r users (almost statistically significant). Among FTC/TDF users, this risk was 8 times higher for LPV/r as compared to EFV.

Overall
Among TDF users

No TDF vs. TDF/FTC
PI vs. NNRTI
LPV vs. EFV

Glomerular filtration rate by CKD‐EPI (mL/min/1.73 m2)

Baseline (median)*
91.6 vs. 93.7
90.7 vs. 95.7
93.7 vs. 95.8

Month 12 (median)*
98.0 vs. 95.1
89.2 vs. 96.7
71.2 vs. 97.8 (p < 0.05)

Renal deterioration:

Cases (n, %)
4/38 (10.5%) vs. 9/79 (11.4%)
5/33 (15.1) vs. 4/45 (8.9)
4/21 (19.0) vs. 3/40 (7.5)

Log rank (time to event)
0.883
0.278
0.055

Crude HR (95% CI)
1.09 (0.34, 3.55)
2.06 (0.54, 7.86)
3.96 (0.87, 17.93)

Adjusted HR** (95% CI)
0.60 (0.15, 2.35)
3.37 (0.76, 14.87)
8.20 (1.30, 51.75)

All comparisons between arms, and between baseline and month 24 were not statistically significant unless otherwise indicated.
Adjusted by age, sex, transmission category and baseline CD4 count and viral load.