Short Communication: Resolution of Tenofovir Disoproxil Fumarate Induced Fanconi Syndrome with Switch to Tenofovir Alafenamide Fumarate in a HIV-1 and Hepatitis B Coinfected Patient

Abstract

Fanconi syndrome is a rare adverse effect of tenofovir disoproxil fumarate (TDF). Tenofovir alafenamide fumarate (TAF) is a novel prodrug with less nephrotoxicity. We report resolution of Fanconi syndrome in a HIV and hepatitis B coinfected patient switched from TDF to TAF.

Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

“…In one of the registration trials, a slight drop (0.1 mg/dL) in serum phosphate was seen in HBeAg‐positive CHB receiving TAF, whereas no change was observed among TDF at week 48 . A mono‐infected CHB patient who had Fanconi syndrome on TDF showed stabilization (but no improvement) of renal tubular function including TMPO4 after being switched to TAF . These findings suggest that bone changes as a result of long‐term TDF use may not be due entirely to urinary phosphate loss but rather a direct TDF effect on bone metabolism.…”

“…23 A mono-infected CHB patient who had Fanconi syndrome on TDF showed stabilization (but no improvement) of renal tubular function including TMPO4 after being switched to TAF. 28,29 These findings suggest that bone changes as a result of long-term TDF use may not be due entirely to urinary phosphate loss but rather a direct TDF effect on bone metabolism. Indeed, using in vitro models, it has been shown that TDF directly impairs rat osteoblast function 30 and human osteoblast mineralization.…”

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

“…While these data suggest that there were no immediate demonstrable adverse effects of TAF on kidney function, longer term safety data are required to confirm the safety of TAF in this vulnerable group of patients, and hence this study will continue to follow all participants until at least 96 weeks. Clinical trial data suggest that TAF may be a suitable option for people with HIV infection who have mild-tomoderate CKD, [11] and, while some case reports suggest that TAF may also be an option for those who experienced treatment-limiting PRT on TDF, [12][13][14][15] others have reported acute kidney injury (AKI) with and without tubular function abnormalities in selected individuals receiving TAF [19][20][21][22]. While these cases raise the possibility of TAF nephrotoxicity, in one case the patient took an overdose (300 mg of TAF among other compounds); the second patient had liver cirrhosis and diabetes, actively used heroin and cocaine, had multiple co-medications and presented with AKI and nephrotic syndrome; the third patient had decompensated liver cirrhosis, actively used alcohol, underwent treatment for hepatitis and also presented with AKI and nephrotic syndrome; and the fourth patient presented with AKI shortly after switching from TDF, which he had tolerated for the past 10 years, each suggesting that other factors could have contributed to and/or were responsible for the kidney injury.…”

“…Individuals who developed PRT while receiving TDF, however, may be uniquely susceptible to the adverse effects of tenofovir on the kidneys and bone. While TAF has been used in a small number of individuals who developed PRT on TDF , it remains to be confirmed whether TAF can be used safely in this group of patients.…”

HIV update: Impact on chronic diseases

“…[39][40][41] A recent report even describes the resolution of Fanconi syndrome upon changing from TDF to TAF. 42 Current practice guidelines include both prodrugs as options for treatment of HIV and also HBV, 12,43 but the lower frequency of bone and renal toxicity makes TAF a more favorable option for management of these infections. TDF still has an advantage over TAF in that Descovy (the TAF version of Truvada) has not been approved for prevention of HIV infection (pre-exposure prophylaxis).…”