Safety of Tenofovir Alafenamide in People With HIV Who Experienced Proximal Renal Tubulopathy on Tenofovir Disoproxil Fumarate.

BACKGROUND:Proximal renal tubulopathy (PRT) is an infrequent complication of tenofovir disoproxil fumarate (TDF). It remains to be established whether tenofovir alafenamide (TAF) can be safely administered to individuals who experienced PRT on TDF. METHODS:Individuals with a history of TDF-associated PRT and current estimated glomerular filtration rate (eGFR) over 30 mL/min/1.73 m2 initiated TAF and were followed for 96 weeks. The primary outcome of interest was recurrent PRT. Secondary outcomes were changes in kidney biomarkers, bone biomarkers, and bone mineral density (BMD). Data were analyzed using multilevel mixed-effects linear regression models. The trial was registered under EudraCT 2016-003345-29. RESULTS:All 31 participants [median age 55 (inter-quartile range 51, 60) years, 97% men, 87% White ethnicity] remained on TAF at week 96, and none developed glycosuria or recurrent PRT. Participants experienced small declines in eGFR-creatinine [-1.9 (95% confidence interval: -3.5 to -0.3) mL/min/1.73 m2/yr; P = 0.024], but not in eGFR-cystatin C [-0.9 (-2.1 to 0.4) mL/min/1.73 m2/yr; P = 0.16]. Ten (32%) and 5 (16%) participants experienced rapid (>5 mL/min/1.73 m2/yr) decline in eGFR-creatinine and eGFR-cystatin C. No significant change in other kidney biomarkers, bone turnover, or BMD was observed (P > 0.2). CONCLUSIONS:In individuals with a history of PRT on TDF, 96 weeks of TAF was not associated with recurrent PRT or adverse effects on renal tubular function, bone turnover, or BMD. These data suggest that TAF is a treatment option for this vulnerable population.