(249) Tenofovir alafenamide versus non-tenofovir alafenamide-containing antiretroviral regimens and the effects on changes of proteinuria biomarkers in the treatment of human immunodeficiency virus type 1: a systematic literature review and meta-analysis

Background: : Excessive accumulation of tenofovir disoproxil fumarate in proximal tubular cells can cause proteinuria. Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), is associated with improved renal outcomes.

Objective: : To compare changes of proteinuria biomarkers between TAF- and non-TAF-based antiretroviral regimens (ARTs).

Methods: : A comprehensive search in PubMed, Embase, Web of Science, and Cochrane Library was conducted from inception through 07/17/2025. Eligible studies were randomized controlled trials (RCTs) comparing TAF vs non-TAF ART for HIV-1 treatment and reported changes in Urine Protein-to-Creatinine Ratio (UPCR), Urine Albumin-to-Creatinine Ratio (UACR), Urinary Retinol-Binding Protein-to-Creatinine Ratio (RBPCR), Urinary Beta-2 Microglobulin-to-Creatinine Ratio (b2MCR). Outcomes were pooled by mean difference (MD) and 95% confidence intervals (95% CI) in a random-effects model. I2 was used to assess heterogeneity. The primary analysis included longest follow-up for each RCT whereas the subgroup focused exclusively on results presented at 48 weeks post treatment initiation.

Results: : We included 11 studies for UPCR (n=7143, 14 for UACR (n=7823), 17 for RBPCR (n=7819) and 16 for b2MCR (n=8719). TAF was associated with significantly better outcomes in terms of absolute value changes (UPCR: -12.8mg/g, [-18.9; -1.46], I2=84.7%; UCAR: -0.86mg/g, [-1.31; -0.41], I2=72.8%; RBPCR: -45.71ug/g, [-62.56; -28.86], I2=77.7%; b2MCR: -41.63ug/g, [-58.55, -24.72], I2=89.8%) and percentage changes (UPCR: -23.7%, [-34.49; -12.92], I2=85.4%; UCAR: -18.66%, [-28; -9.32], I2=82.8%; RBPCR: -29.5%, [-37.3; -21.71], I2=99.3%; b2MCR: -39.18%, [-55.78, -22.58], I2=94.4%) of all proteinuria biomarkers compared to non-TAF regimens in the primary analyses. The trend in effect sizes of absolute value changes (UPCR: -6.26mg/g, [-24.71; 12.18], I2=90.3%; UACR: -0.24mg/g, [-0.88; 0.39], I2=68.8%; RBPCR: -10.97ug/g, [-23.6, 1.66], I2=99.9%; b2MCR: -7.17ug/g, [-13.91; -0.42], I2=59.3%) and percentage changes (UPCR: -12%, [-47.6; 23.61], I2=90.1%; UACR: -17.56%, [-38.12, 2.99], I2=84.9%;RBPCR: -7.55%, [-14.46; -0.64], I2=62.6%; b2MCR: -5.43%, [-10.63; -0.24], I2=65.8%) were consistent in the subgroup analyses at week 48 with non-TFV comparators. High heterogeneity was observed, and further subgroup analyses will be reported to investigate these differences.

Conclusions: : TAF-based regimens showed greater reductions in proteinuria biomarkers than non-TAF regimens. By week 48, the direction of effect remained consistent with non-TFV-based comparators, though statistical significance was not observed.

Sponsorship:: Gilead Sciences