Estimated Glomerular Filtration Rate Slopes on Tenofovir Alafenamide

F Ibrahim; L Campbell; AC Bailey; S Stockwell; L Waters; C Orkin; M Johnson; M Gompels; A De Burgh-Thomas; R Jones; G Schembri; PW Mallon; FA Post

Disclosures

HIV Medicine. 2020;21(9):607-612. 

In This Article

Discussion

Our study demonstrates that eGFR slopes improved in individuals who switched from TDF- to TAF-containing ART, particularly in those who experienced rapid eGFR decline or CKD while receiving TDF. These data expand clinical trial experience which has shown that TAF is associated with stable renal function, even in those with mild/moderate CKD, and a more favourable renal biomarker profile than TDF.[12,13] Moreover, TAF had been successfully used and was shown to have no significant effect on biomarkers of renal tubular function in individuals who experienced proximal tubulopathy/Fanconi syndrome while receiving TDF,[16–20] suggesting that the renal safety of TAF extends to a broad population of people with HIV infection.

In this observational study, eGFR decline during TDF use improved, and in some cases resolved, with switching from TDF to TAF, suggesting that in many cases the observed eGFR decline may have been caused, or at least contributed to, by TDF. The somewhat greater eGFR decline during TDF exposure in those who discontinued TDF prior to TAF initiation as compared to those who directly switched from TDF to TAF probably reflects a greater proportion of renal discontinuations and/or more pronounced adverse effects of tenofovir on the kidney in the former group. In settings such as the UK, where TDF remains the tenofovir formulation of choice for people without established CKD or bone fragility, safety monitoring should include review of trends in renal function (eGFR and proteinuria).[21] Individuals who experience progressive eGFR decline or worsening proteinuria while receiving TDF should discontinue this drug to avoid further worsening of kidney function and potential kidney damage.[7] Our study suggests that TAF may be an appropriate option for such patients.

These data should be viewed with several limitations in mind. Identification of early TAF recipients was retrospective, and the median follow-up was relatively short. In addition, data on albuminuria and renal tubular function (low-molecular-weight proteinuria, glycosuria and phosphate wasting) were not (or only sparsely) available. Finally, the health care systems differed between the two participating countries, with limited access to TAF in the UK and unrestricted access in Ireland.

In conclusion, we observed stable or improved eGFR in the vast majority of early TAF recipients, some of whom had renal impairment and/or experienced renal dysfunction while receiving TDF. Our data suggest that rapid decline in eGFR seen in some TDF-treated individuals may be abrogated by switching from TDF to TAF. As eGFR decline may be an early manifestation of proximal renal tubulopathy,[6] switching patients who experience eGFR decline from TDF to TAF may be an attractive strategy to avoid renal tubular injury.

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