Association of Higher Plasma Vitamin D Binding Protein and Lower Free Calcitriol Levels with Tenofovir Disoproxil Fumarate Use and Plasma and Intracellular Tenofovir Pharmacokinetics: Cause of a

Tenofovir disoproxil fumarate (TDF) causes bone, endocrine, and renal changes by anunknownmechanism(s). Data are limited on tenofovir pharmacokinetics and these effects. Using baseline data fromamulticenter study ofHIV-infected youth on stable treatment with regimens containingTDF (n 118) or lackingTDF (n 85), wemeasured cross-sectional associations of TDFusewithmarkers of renal function, vitaminD-calcium-parathyroid hormone balance, phosphatemetabolism (tubular reabsorption of phosphate and fibroblast growth factor 23 [FGF23]), and bone turnover. Pharmacokinetic-pharmacodynamic associationswith plasma tenofovir and intracellular tenofovir diphosphate concentrationswere explored among those receivingTDF. Themean agewas 20.9 (standard devia-tion [SD], 2.0) years; 63%weremale; and 52%wereAfricanAmerican. Compared to the no-TDF group, the TDF group showed lowe