Tenofovir Alafenamide and Tenofovir Disoproxil Fumarate are not transported by Concentrative Nucleoside Transporter 2

Abstract

Tenofovir-associated renal toxicity is influenced by several factors, including plasma exposure and genetic variants in transporter-encoding genes. Tenofovir plasma exposure has been associated with a polymorphism in SLC28A2 gene (encoding the concentrative nucleoside transporter 2, CNT2): particularly, SLC28A2 124 CT/TT genotype patients show higher plasma tenofovir concentrations, compared to CC group. In literature, substrate studies are lacking; for this reason, our aim was to understand if tenofovir and tenofovir-alafenamide are CNT2 substrates. We performed an in vitro study using CNT2 expressing MDCKII cells. We observed that tenofovir and tenofovir-alafenamide are not substrates of CNT2. Tenofovir-alafenamide influx pathway remains to be clarified.

Keywords: CNT2; HAART; HIV; Renal toxicity; SLC28A2; TAF; TDF.