Plasma concentration of neurofilament light chain protein decreases after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate

Autoři: Linn Hermansson aff001;  Aylin Yilmaz aff001;  Richard W. Price aff003;  Staffan Nilsson aff004;  Scott McCallister aff005;  Tariro Makadzange aff005;  Moupali Das aff005;  Henrik Zetterberg aff006;  Kaj Blennow aff005;  Magnus Gisslen aff001
Působiště autorů: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden aff001;  Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden aff002;  Department of Neurology, University of California, San Francisco, United States of America aff003;  Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden aff004;  Gilead Sciences Inc, Institute of Neuroscience and Physiology, Foster City, California, United States of America aff005;  Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden aff006;  Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden aff007;  Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, United Kingdom aff008;  UK Dementia Research Institute, UCL, London, United Kingdom aff009
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article



Because tenofovir alafenamide (TAF) leads to significantly lower plasma tenofovir concentrations than tenofovir disoproxil fumarate (TDF) and is a stronger substrate for P-glycoprotein (P-gp) than TDF, TAF could lead to decreased central nervous system (CNS) tenofovir exposure than TDF. We aimed to determine if switching from TDF to TAF increases the risk of neuronal injury, by quantifying plasma levels of neurofilament light protein (NfL), a sensitive marker of neuronal injury in HIV CNS infection.


Plasma NfL concentration was measured at baseline, week 24, and week 84 in stored plasma samples from 416 participants (272 switching to elvitegravir (E)/cobicistat (C)/emtricitabine (F)/TAF and 144 continuing E/C/F/TDF) enrolled in the randomized, active-controlled, multicenter, open-label, noninferiority Gilead GS-US-292-0109 trial.


While plasma NfL levels in both groups were within the normal range, we found a small but significant decrease in the E/C/F/TAF arm after 84 weeks from a geometric mean of 9.3 to 8.8 pg/mL (5.4% decline, 95% CI 2.0–8.4, p = 0.002). This change was significantly different (p = 0.001) from that of the E/C/F/TDF arm, in which plasma NfL concentration changed from 9.7 pg/mL at baseline to 10.2 pg/mL at week 84 (5.8% increase, 95% CI -0.8–12.9, p = 0.085). This increase is in line with what could be expected in normal ageing. Plasma NfL concentrations significantly correlated with age. No correlation was found between plasma NfL and serum creatinine.


We found no biomarker evidence of CNS injury when switching from TDF to TAF. It is unclear whether the small decrease in plasma NfL found after switch to TAF is of any clinical relevance, particularly with plasma NfL levels in both arms remaining within the limits found in HIV-negative controls. These results indicate that switching from TDF to TAF appears safe with regard to neuronal injury.

Klíčová slova:

Blood plasma – Central nervous system – Cerebrospinal fluid – Creatinine – HIV infections – Immune activation – Macrophages – Plasma proteins


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