CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

828

Safety of Tenofovir Alafenamide in Individuals With a History of Proximal Renal Tubulopathy on TDF Lucy Campbell 1 , Birgit Barbini 1 , Ben Cromarty 2 , Lisa Hamzah 3 , Margaret Johnson 4 , Deborah Williams 5 , Alan Winston 6 , Frank A. Post 7 , for the FANTA Trial Team 1 King's College London, London, United Kingdom, 2 UK Community Advisory Board, London, United Kingdom, 3 St George's University of London, London, United Kingdom, 4 Royal Free Hospital, London, United Kingdom, 5 Brighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom, 6 Imperial College London, London, United Kingdom, 7 King's College Hospital NHS Foundation Trust, London, United Kingdom Background: Proximal renal tubulopathy (PRT, Fanconi syndrome) is an important but uncommon complication of tenofovir disoproxil fumarate (TDF). There are few long-term safety data for tenofovir alafenamide (TAF) in this population. We evaluated the safety of TAF in individuals who experienced treatment-limiting PRT while receiving TDF, and here report the five year outcomes. Methods: Participants with HIV, a history of TDF-associated PRT, an estimated glomerular filtration rate >30 mL/min/1.73m², HIV RNA <200 copies/mL, and who were no longer receiving TDF and naïve to TAF were switched to a TAF-based antiretroviral therapy (ART) regimen and followed up annually for five years. The primary outcome was recurrent PRT. Secondary outcomes were changes in kidney biomarkers, alkaline phosphatase, and bone mineral density (BMD). Data were analysed using multi-level mixed effects linear regression models. The trial was registered under EudraCT 2016-003345-29. Results: Of the 28 study participants (median age 55 [IQR 51, 60] years, 96% male, 86% white ethnicity) who agreed to continued follow up beyond week 96, 26 remained on TAF at year 5. Two participants (7%) discontinued TAF (treatment simplification, pre-emptive switch during critical care unit admission for COVID-19), 2 participants (7%) experienced transient HIV viraemia (200-1000 copies/mL) while all others remained virally suppressed; none experienced recurrent PRT during 134 person-years of follow up. Participants experienced small declines in BMD at the total hip; there were no significant changes in estimated glomerular filtration rate (eGFR-creatinine), albuminuria, proteinuria, fractional excretion of phosphate, alkaline phosphatase, or BMD at the lumbar spine. Conclusion: In individuals with a history of PRT on TDF, cumulative exposure to TAF-based ART for five years was not associated with recurrent PRT or adverse effects on renal function or BMD. These data suggest that TAF is a safe treatment option for this vulnerable population.

pre-selected panel of miRs were isolated and quantified using miR-specific real-time qPCR. Results: At inclusion, median time on TDF was 65 months (38-82.6), and mean eGFR was 90.9 ml/min/1.73m 2 (50.1-122; only 6% of patients with chronic kidney disease CKD diagnosis). A profile of 7 miRs were evaluated. The levels of miR-let-7d, miR-203, and miR-29a were significantly upregulated (p=0.018, and p=0.014) according to time on TDF, while miR-127 was negatively correlated (p=0.033). Moreover, miR-Let-7-d miR-107, and miR-23a positively correlated with tubular and biomarkers parameters, such as fractional excretion of phosphate, glycosuria, albumin/creatinine, β2-microglobuline/creatinine, RBP/creatinine, and protein/creatinine ratios. Thus, miR-let-7d, miR-107, and miR-423 were found to have increased expression in patients with tubular dysfunction and miR-15b was upregulated in urinary exosomes of patients with decreased eGFR (p=0.028). An increased expression of miR-let-7d predict tubular dysfunction (AUC 0.733), and miR-23a identified those with subsequent eGFR decrease (AUC 0.633), respectively, after a median follow up of 9 months (IQR, 4-13). Conclusion: This is the first study showing the usefulness of micro-RNA as biomarkers of antiretroviral drug-associated toxicity. Specifically, the expression profile of miRs was significantly altered in urinary exosomes according to time on TDF, changes in tubular parameters and presence of tubular dysfunction, and were associated with further tubular dysfunction and eGFR decrease. Thus, this study confirms that exosome-derived miRs in urine could be used as non invasive biomarkers for the detection of renal toxicity associated with TDF. Biomarkers Influence Kidney Function Estimates More So Than Race Among Persons With HIV Peggy-Ita A Obeng-Nyarkoh 1 , Amanda B. Spence 1 , Richard Teran 2 , Christopher A. Loffredo 1 , Bruce Luxon 1 , Joseph Timpone 1 , Princy Kumar 1 , Jason Umans 3 , Seble Kassaye 1 1 Georgetown University, Washington, DC, USA, 2 Centers for Disease Control and Prevention, Atlanta, GA, USA, 3 MedStar Health Research Institute, Hyattsville, MD, USA Background: Kidney function estimation equations were revised in 2021 to exclude race, refuting earlier assumptions that creatinine (Cr), a by-product of muscle metabolism, consistently differs by race. Cystatin C (CysC) is a biomarker produced by nucleated cells and can be used in conjunction with creatinine to estimate kidney function. We sought to understand the effects of different estimating equations and biomarkers on Chronic Kidney Disease (CKD) stage estimates among persons with HIV (PWH), for whom CKD is an important comorbidity. Methods: CysC and Cr was measured in this cross-sectional single site U.S. clinic-based study from 2014-2016. The 2009 CKD-EPI-Cr and 2012 CKD-EPI Cr-CysC (which include race), and 2021 CKD-EPI-Cr and 2021 CKD-EPI-Cr-CysC (which exclude race) estimating equations were applied to categorize CKD stage, and agreement was assessed using differences of proportions. Regression analyses evaluated factors associated with CKD stage, and the Breslow-Day test evaluated whether race served as an effect modifier. Results: Among 306 PWH, the median age was 48.2 years, 86 (28.1%) were female,185 (60.5%) were Black,91 (29.7%) Caucasian,13 (4.3%) Latinx, and 46 (15%) had HCV co-infection. The median CD4+ count was 659/mm 3 , 97.7% were on ART, and 74.5% had HIV VL < 20 c/mL. Using the 2009 and 2012 equations (including race), more individuals were categorized as having normal kidney function (Stage I) with inclusion of CysC than Cr alone (73.2% vs 54.6%, p<0.00001); fewer individuals were classified in CKD stages III-V using CysC than Cr alone, but this did not meet statistical significance (8.2% vs 11.8%, p=0.14). Using 2021 equations (excluding race) a larger proportion were classified as normal kidney function with inclusion of CysC than Cr alone (73.8% vs 49.3%, p=0. 0.00001); fewer were categorized as CKD III-V with inclusion of CysC than Cr alone (8.1% vs 13.1%, p=0.026). Multivariate linear regression identified age, the interaction between tobacco use and absolute CD4+ count, and the interaction between HCV co-infection and nadir CD4+ count as factors associated with kidney function. Race was not an effect modifier based on our analyses. Conclusion: Among PWH, CysC shifted estimates of kidney function towards normal and resulted in shifts in kidney function categorization much more so than the small race effect. As some antiretrovirals raise creatinine without affecting renal function, CysC remains an important but under-utilized biomarker to confirm diminished kidney function.

Poster Abstracts

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829

Urinary Exosome-Derived MicroRNAs as Biomarkers of TDF Renal Toxicity in People Living With HIV Jose L. Casado, Isabel Izuzquiza, Pilar Vizcarra, Carmen Santiuste, Jose M. Del Rey, Alejandro Vallejo Hospital Ramón y Cajal, Madrid, Spain Background: The use of tenofovir disoproxil fumarate (TDF) may produce tubular proximal renal toxicity, but severity and outcome is controversial and specific biomarkers are still required. The aim of this study was to evaluate the expression profiles of urinary exosome-derived microRNA (miR) as biomarkers of TDF-associated renal toxicity. Methods: In a longitudinal study, urine samples from 60 virologically suppressed people living with HIV (PWH) receiving TDF were collected. In all cases, different tubular parameters and urinary low-weight molecular proteins (LWMP, beta-2-microglobulin, retinol-binding protein) were compared according to mRNA analyzed. Tubular dysfunction was defined as the presence of at least 2 tubular abnormalities. Urine exosomes were precipitated and a

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