Campbell L, Barbini B, Burling K, et al; FANTA trial team. Safety of tenofovir alafenamide in people with HIV who experienced proximal renal tubulopathy on tenofovir disoproxil fumarate. J Acquir Immune Defic Syndr. 2021 Oct 1; 88(2): 214-219. doi: 10.1097/QAI.0000000000002747. PMID: 34506361.
This study describes 96-week findings of an open-label, single-arm phase 4 trial to assess whether tenofovir alafenamide (TAF) exposure led to recurrent proximal renal tubulopathy (PRT) among 31 adults with HIV and a history of treatment-limiting PRT or Fanconi syndrome on tenofovir disoproxil fumarate (TDF). Participants were virologically suppressed on stable ART; people with diabetes mellitus, 1+ or greater glycosuria, 2+ or greater proteinuria, urine PCR ≥ 100 mg/mmol, or creatinine clearance < 30 mL/min were ineligible. Biomarker evaluation was conducted at multiple points after randomization to immediate or deferred initiation of once daily co-formulated emtricitabine/TAF. At week 96, all 31 participants remained on F/TAF and no one developed PRT, although investigators noted continued proteinuria from baseline (PCR > 30 mg/mmol) in 3 participants; single-episode hypophosphatemia in 2 (resolved by week 96); and no dipstick glycosuria. Ten (32%) and 5 (16%) participants experienced rapid (> 5 mL/min/1.73 m2/yr) decline in eGFR-creatinine and eGFR-cystatin C, respectively. Secondary outcomes analyses found no significant change in other renal biomarker profiles, increases in 25(OH)D concentration, and no significant changes in BMD at the lumbar spine, femoral neck, and hip.
Case reports have described mixed outcomes of TAF exposure in people with a history of kidney injury on TDF. This case series involving a relatively robust renal and bone biomarker evaluation for over 30 participants is a welcome one, given ongoing widespread TDF use for both HIV treatment and prevention. Although it lacked a control group, overall findings seem fairly reassuring: none of the participants developed recurrent PRT, glycosuria, sustained hypophosphatemia, or worsening total proteinuria over 96 weeks. Additionally, eGFR-cystatin C measurements were stable although small declines in eGFR-creatinine were noted (the rapid decline experienced by a subset of participants bears further inquiry). People with a history of TDF-associated kidney injury and providers may be pleased to note TAF might remain a viable option as suggested by authors. Future results from ongoing follow-up of this cohort (and from additional studies involving other, more generalizable cohorts), if also favorable, may increase interest and confidence in this option.