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Abstract: TH-PO1073

Proteinuria Outcomes of Tenofovir Alafenamide Fumarate (TAF) vs. Tenofovir Disoproxil Fumarate (TDF) Regimens for Treatment of HIV, HBV, and HIV PrEP: A Systematic Literature Review and Meta-Analysis

Session Information

Category: CKD (Non-Dialysis)

  • 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Liang, Xi, University of Utah Health, Salt Lake City, Utah, United States
  • Park, Kyu Yun, University of Utah Health, Salt Lake City, Utah, United States
  • Lee, Haeseon, University of Utah Health, Salt Lake City, Utah, United States
  • Chaiyakunapruk, Nathorn, University of Utah Health, Salt Lake City, Utah, United States
  • Dhippayom, Tara, The Prince Royal's College, Chiang Mai, Thailand
  • Rogers, Rachel, Gilead Sciences Inc, Foster City, California, United States
  • Weinberg, Amy R., Gilead Sciences Inc, Foster City, California, United States
  • Green, Julia, Gilead Sciences Inc, Foster City, California, United States
  • Chi, Aileen, Gilead Sciences Inc, Foster City, California, United States
  • Willis, Connor W., University of Utah Health, Salt Lake City, Utah, United States
Background

TDF and TAF are tenofovir’s prodrugs. TAF has improved renal safety and comparable efficacy to TDF. Monitoring proteinuria biomarkers is crucial for early kidney damage detection. We aimed to comprehensively synthesize evidence on proteinuria outcomes of TDF and TAF regimens.

Methods

We systematically reviewed RCTs comparing TDF vs. TAF for pre-exposure prophylaxis (PrEP), treatment of human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), and HIV/HBV. We searched PubMed, EMBASE, Web of Science, and Cochrane Trial Registry from inception to 12/6/2023. The outcomes were pooled using mean % change differences with 95% CI. The heterogeneity was assessed using I2 test. Subgroup analyses were based on baseline eGFR and prior treatment.

Results

Out of 9,014 studies, 10 RCTs reported urine protein to creatinine ratio (UPCR), 12 RCTs reported urine albumin to creatinine ratio (UACR), 15 RCTs reported retinol-binding protein to creatinine ratio (RBPCR), and 16 RCTs reported β2-macroglobulin to creatinine ratio (β2MCR). TAF showed improved proteinuria compared to TDF, with a magnitude of improvement increasing over time. This trend was consistent across all subgroup analyses.

Conclusion

Proteinuria outcomes significantly improved with TAF compared to TDF, which became more pronounced over time. This supports using TAF regimens across indications.

Effect Sizes and Heterogeneity of Changes in Proteinuria Biomarkers of TAF Compared to TDF
 Effect sizes† (95% CI)I2
Proteinuria (no. participants in TAF, TDF)Week 24Week 48Week 96Week 144Week 24Week 48Week 96Week 144
UPCR (3720, 2991)-15.48
(-40.90 to -9.93)		-22.91
(-31.26 to -14.55)		-26.55
(-35.54 to -17.56)		N/A83.58%67.93%0%N/A
UACR (4458, 3729)-10.50
(-24.99 to 3.99)		-16.42
(-21.99 to -10.84)		-17.84
(-27.14 to -8.55)		N/AN/A*38.78%74.76%N/A
RBPCR (7177, 6653)N/A-38.09
(-47.14 to -29.03)		-48.94
(-69.52 to -28.35)		-50.78
(-90.03 to -11.53)		N/A42.82%68.26%60.21%
β2MCR (7372, 6889)-19.70
(-33.09 to -4.31)		-47.69
(-60.30 to -35.07)		-59.11
(-85.49 to -32.73)		-55.31
(-83.10 to -27.52)		N/A*55.54%64.71%23.52%

† TAF’s comparative % change from baseline to that of TDF *Only 1 study included. Thus, heterogeneity is not available.

Comparative Reduction of Proteinuria Biomarkers of TAF to TDF

Funding

  • Commercial Support – Gilead Sciences, Inc.