Background: Tenofovir disoproxil fumarate is a prodrug of tenofovir diphosphate that exposes patients to renal toxicity over the long term. Tenofovir alafenamide, a new prodrug, now makes it possible to reduce toxicity, but at the cost of an alteration in lipid profile. There is currently no recommendation for follow-up of lipid profile when switching from tenofovir disoproxil fumarate to tenofovir alafenamide. Objective: Our study aimed to evaluate the effects on renal function and lipid profile of a switch from tenofovir disoproxil fumarate to tenofovir alafenamide, and the consequences for patient management. Methods: Demographic, clinical and biological data was recorded from a retrospective clinical cohort study in real-life, including patients who switched from tenofovir disoproxil fumarate to tenofovir alafenamide. A descriptive analysis of the study population, with comparison of biological parameters using the paired Student t test for paired data was performed. Results: From January 2016 to January 2019, a total of 103 patients were included. There was no significant difference in renal function before vs after the switch in therapy (p=0.29 for creatinine, p=0.30 for phosphoremia). We observed a change in lipid profile, with a significant increase in total cholesterol (p=0.0006), HDL cholesterol (p=0.0055) and triglycerides (p=0.0242). Four patients received lipid-lowering therapy after switching. Conclusion: In patients who switch from tenofovir disoproxil fumarate to tenofovir alafenamide, lipid profile is altered, and may require initiation of lipid-lowering therapy. It seems necessary to monitor lipid parameters after this switch, despite the absence of an official recommendation.

Background In oncology, liquid biopsy is of major relevance from theranostic point of view. The searching for mutations in circulating tumor DNA (ctDNA) in case of colorectal cancers (CRCs) allows the optimization of patient care. In this context, independent of mutation status biomarkers are required for its detection to confirm the presence of ctDNA in liquid biopsies. Indeed, the hypermethylation of NPY and WIF1 genes appear to be an ideal biomarker for the specific detection of ctDNA in CRCs. The objective of this work is to develop the research of hypermethylation of NPY and WIF1 by Crystal Digital PCR™ for the detection of ctDNA in CRCs. Methods Detection of hypermethylated NPY and WIF1 was developed on Cristal digital PCR™. Biological validation was performed from a local cohort of 22 liquid biopsies and 23 tissue samples from patients with CRC. These patients were treated at the University Hospital of Besancon (France). Results The local cohort study confirmed that NPY and WIF1 were significantly hypermethylated in tumor tissues compared to adjacent non-tumor tissues (WIF1 p < 0.001; NPY p < 0.001; non-parametric Wilcoxon paired-series test). Histological characteristics, tumor stages or mutation status were not correlated to the methylation profiles. On the other hand, hypermethylation of NPY or WIF1 in liquid biopsy had a 95.5% [95%CI 77–100%] sensitivity and 100% [95%CI 69–100%] specificity. Conclusion Using Crystal digital PCR™, this study shows that hypermethylation of NPY and WIF1 are constant specific biomarkers of CRCs regardless of a potential role in carcinogenesis.

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