Tenofovir (TFV) is an acyclic nucleotide analog of dAMP, a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) replication, although with low cellular permeability and oral bioavailability. In order to improve its pharmacological profile, prodrugs of TFV have been synthesized, such as tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF). The pharmacological advantages provided by TAF are attributed to its activation mechanism, which is related to the serine protease cathepsin A (CTSA), a component of a high-molecular weight complex of lysosomal-galactosidase and N-acetyl neuraminidase. CTSA is expressed by a broad range of human tissues, including kidney, liver, macrophages, platelets, and testis. In the present study, we have determined the level of CTSA expression in CD4+ T cells from HIV-positive patients, correlating it to the viral set point, and its modulation upon antiretroviral treatment initiation.

Our data show CTSA is constitutively expressed in CD4+ T cells from high-viremic patients, low viremic patients, elite controllers (EC) and healthy donors, with a non-significant trend towards higher viral set point, being CTSA lower in the CD4+ T cells from EC. ART initiation did not change the expression levels of CTSA.