Assessing Renal Outcomes After Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People with HIV: Proteinuria Changes and Limits of Causal Attribution.
5 affiliations
- 1Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy.
- 2Tumor Immunology Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Corso Tukory 211, 90134 Palermo, Italy.
- 3Legal Medicine Unit, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127 Palermo, Italy.
- 4Infectious and Tropical Diseases Unit, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127 Palermo, Italy.
- 5Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy.
Abstract
Background: The total urinary protein-to-creatinine ratio (PCr) measures proteinuria but does not establish tubular injury or its recovery. Methods: We examined PCr changes after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in a single-centre retrospective cohort of 364 adults with human immunodeficiency virus (HIV) infection. Paired PCr values were available for 159 patients (43.7%). The primary descriptive endpoint was a PCr reduction below 20%, an operational, nonvalidated threshold. Analyses comprised paired rank-based comparisons, baseline-adjusted regression, threshold and influence sensitivity analyses, and nested cross-validation of ridge logistic regression using three predictor sets. Results: The median paired PCr change was -4.0 mg/g (interquartile range -41.5 to 11.5; signed-rank Benjamini-Hochberg-adjusted q = 0.0098); 99/159 patients (62.3%) had a reduction below 20%. Baseline log(1 + PCr) was positively associated with post-switch log(1 + PCr), while its coefficient in the corresponding change model was exactly one unit lower, illustrating mathematical coupling. The cross-validated area under the curve was 0.709 for baseline PCr alone, 0.475 for the other covariates, and 0.701 for all predictors. Conclusions: PCr changes were heterogeneous, and additional covariates did not improve discrimination over the baseline PCr alone. Missing outcomes, unavailable specimen dates, the absence of tubular-specific biomarkers and the uncontrolled design preclude conclusions about irreversible tubular injury, causal treatment effects or clinical prediction utility.
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BibTeX
@article{danna2026assessing,
title = {{Assessing Renal Outcomes After Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People with HIV: Proteinuria Changes and Limits of Causal Attribution.}},
author = {Tommaso D'Anna and Marcello Trizzino and Beatrice Belmonte and Claudia Gioè and Augusto Orlandi and Stefania Zerbo and Andrea Cicero and Antonina Argo and Antonio Cascio},
journal = {Diseases (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/diseases14100353},
url = {https://europepmc.org/article/MED/42929980},
note = {CC BY},
}
RIS
TY - JOUR
TI - Assessing Renal Outcomes After Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People with HIV: Proteinuria Changes and Limits of Causal Attribution.
AU - Tommaso D'Anna
AU - Marcello Trizzino
AU - Beatrice Belmonte
AU - Claudia Gioè
AU - Augusto Orlandi
AU - Stefania Zerbo
AU - Andrea Cicero
AU - Antonina Argo
AU - Antonio Cascio
PY - 2026
DA - 2026/09/24
JO - Diseases (Basel, Switzerland)
DO - 10.3390/diseases14100353
UR - https://europepmc.org/article/MED/42929980
AB - Background: The total urinary protein-to-creatinine ratio (PCr) measures proteinuria but does not establish tubular injury or its recovery. Methods: We examined PCr changes after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in a single-centre retrospective cohort of 364 adults with human immunodeficiency virus (HIV) infection. Paired PCr values were available for 159 patients (43.7%). The primary descriptive endpoint was a PCr reduction below 20%, an operational, nonvalidated threshold. Analyses comprised paired rank-based comparisons, baseline-adjusted regression, threshold and influence sensitivity analyses, and nested cross-validation of ridge logistic regression using three predictor sets. Results: The median paired PCr change was -4.0 mg/g (interquartile range -41.5 to 11.5; signed-rank Benjamini-Hochberg-adjusted q = 0.0098); 99/159 patients (62.3%) had a reduction below 20%. Baseline log(1 + PCr) was positively associated with post-switch log(1 + PCr), while its coefficient in the corresponding change model was exactly one unit lower, illustrating mathematical coupling. The cross-validated area under the curve was 0.709 for baseline PCr alone, 0.475 for the other covariates, and 0.701 for all predictors. Conclusions: PCr changes were heterogeneous, and additional covariates did not improve discrimination over the baseline PCr alone. Missing outcomes, unavailable specimen dates, the absence of tubular-specific biomarkers and the uncontrolled design preclude conclusions about irreversible tubular injury, causal treatment effects or clinical prediction utility.
SN - 2079-9721
ER -