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Renal Safety of Tenofovir Alafenamide in Patients at High Risk of Kidney Disease
David Wohl1; Anders Thalme2; Robert Finlayson3; Shinichi Oka4; Thai Nguyen5; Susan Guo5; Andrew Cheng5; Moupali Das5; Marshall Fordyce5
1Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA;2Karolinska Inst, Stockholm, Sweden;3Taylor Square Private Clinic, Sydney, Australia;4Natl Cntr for Global Hlth and Med, Tokyo, Japan;5Gilead Sciences, Foster City, CA, USA
Compared with TDF, tenofovir alafenamide (TAF) results in significantly reduced plasma tenofovir (TFV) and has demonstrated less impact on surrogate markers of renal and bone health in multiple populations, but renal outcomes in treatment-naïve subjects at risk for chronic kidney disease (CKD) have not been characterized.
Treatment naïve HIV-1+ adults were randomized 1:1 to a single tablet regimen of elvitegravir, cobicistat, emtricitabine, with tenofovir alafenamide (E/C/F/TAF) or tenofovir disoproxil fumarate (E/C/F/TDF) once daily in two double blind studies. Assessments of renal function included serum creatinine and estimated GFR by Cockcroft-Gault (eGFRCG), and 4 measures of proteinuria: urine protein:creatinine (UPCR), urine albumin:creatinine (UACR), retinol binding protein:creatinine (uRBP:Cr), and beta-2-microglobulin:creatinine (uB2M:Cr). A post-hoc analysis of renal function by group with high risk vs low risk for development of CKD is described. High risk is defined as ≥2 renal risk factors: female gender, age >=50 years, black race, use of NSAIDs, CD4 < 200 cells/uL, history of dyslipidemia, hypertension, diabetes, and clinical or subclinical renal events. Low CKD risk is defined as ≤1 risk factor.
Combined, the two studies randomized and treated 1,733 participants. The proportion of participants with high CKD risk was similar by treatment arm (E/C/F/TAF 28%, E/C/F/TDF 32%). Among high CKD risk participants, significantly fewer subjects on E/C/F/TAF experienced a decline in eGFR to below 60 mL/min compared to E/C/F/TDF: 4.9% vs 9.6% (p=0.044). Participants with high CKD risk who initiated E/C/F/TAF also had significant declines in multiple measures of quantitative proteinuria (Table). Within the low CKD risk group, significantly fewer participants receiving E/C/F/TAF experienced a decline in eGFR by ≥25% (11.5% vs 24.9%, p<0.001). High rates of virologic suppression at week 48 were observed in both treatment groups in the high CKD risk category.
Among participants with both low and high CKD risk, participants receiving E/C/F/TAF had more favorable renal outcomes compared with those treated with E/C/F/TDF. These data provide further support for the improved renal safety profile of TAF.