Long-Term Evaluation of Changes in Kidney Function after Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Patients Living with HIV

Abstract

Tenofovir is one of the most widely used medications for HIV treatment and is administered as either tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). Use of TAF is preferred as it is associated with fewer negative impacts on renal function; however, long-term follow-up beyond 96 weeks is limited. A retrospective chart review of patients ≥18 years who received TDF-containing anti-retroviral therapy (ART) for ≥6 months and then switched to a TAF-containing regimen between 1 December 2015 and 1 January 2020 is presented. The primary objective was to evaluate changes in kidney function as measured by eGFR and Scr. The secondary objective was to evaluate changes in lipids. Among the 142 patients identified, the median age was 66 years old with a median follow-up of 3.6 years. The change in kidney function was a median increase in Scr of 0.1 mg/dL and a decrease in eGFR of −8 mL/min/1.73 m2. The change in lipid panels at the end of the medication use evaluation endpoint was a decrease in total cholesterol, LDL, HDL, and triglycerides of −2.5, −0.1, −0.6, and −9 mmol/L, respectively. There was no clinically meaningful difference in kidney function as measured by eGFR or Scr, nor was there any clinically meaningful difference in lipid panels in patients switched from TDF to TAF-containing ART. Our observations suggest that the favorable impact of TAF on kidney function is sustained for at least 44 months after conversion from TDF.

Tenofovir-Associated Kidney Dysfunction and Bone Fracture: A Case Report and Literature Review

“…According to the European guidelines, patients on TDF with eGFR less than 60 mL/minute should be offered an alternate regimen if their eGFR falls by 5 mL/year for three consecutive years or more than 25% from the baseline. National Institutes of Health (NIH) guidelines recommend cautious use or avoidance of TDF in patients with existing kidney impairment [ 7 ].…”

“…In a randomized controlled trial conducted among 441 patients by Martin et al [ 18 ], comparing tenofovir-emtricitabine (TDF-FTC) and abacavir-lamivudine (ABC-3TC) at weeks 48 and 96, the former group demonstrated markedly decreased hip and spine t scores and had developed skeletal lesions such as osteopenia or osteoporosis or received antiresorptive therapy, while among the latter group, a rise in both t scores was noted. A higher incidence rate of osteonecrosis of the femur has been reported in retropositive patients, which is around 100 times higher than the anticipated incidence in the general population [ 7 ].…”

Tenofovir-Induced Renal Dysfunction Among HIV-Infected Patients: A Systematic Review

“…Tenofovir accumulates within cells because of increased entry from the human organic anion transporters (OAT1 and OAT3) and decreased efflux into the tubular lumen, which is the primary mechanism of TDF-induced nephrotoxicity [ 5 ]. TAF is a prodrug that absorbs more rapidly than TDF and causes cells to produce more tenofovir diphosphate, the drug’s active ingredient [ 5 ].…”

“…According to a study conducted among more than 10,000 HIV-positive patients, the chance of developing CKD, proteinuria, and rapidly deteriorating kidney function increased by 34%, 11%, and 33%, respectively, for every year of exposure to TDF [ 5 ]. The rules of European societies recommend that patients using TDF with an estimated glomerular filtration rate (eGFR) of more than 60 mL/minute be given the option to switch medications if their eGFR has dropped more than 25% from baseline and/or has decreased by 5 mL/year for three or more years [ 5 ]. They also concur with the National Institutes of Health (NIH) guidelines that patients with baseline renal disease should use TDF cautiously or not at all [ 5 ].…”

“…The rules of European societies recommend that patients using TDF with an estimated glomerular filtration rate (eGFR) of more than 60 mL/minute be given the option to switch medications if their eGFR has dropped more than 25% from baseline and/or has decreased by 5 mL/year for three or more years [ 5 ]. They also concur with the National Institutes of Health (NIH) guidelines that patients with baseline renal disease should use TDF cautiously or not at all [ 5 ].…”