Plasma concentration of neurofilament light chain protein decreases after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate
Artikel i vetenskaplig tidskrift, 2019

Background 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. Methods 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. Results 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. Conclusions 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.

Författare

Linn Hermansson

Göteborgs universitet

Sahlgrenska universitetssjukhuset

Aylin Yilmaz

Sahlgrenska universitetssjukhuset

Göteborgs universitet

R.W. Price

University of California

Staffan Nilsson

Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik

Scott McCallister

Gilead Sciences Incorporated

Tariro Makadzange

Gilead Sciences Incorporated

Moupali Das

Gilead Sciences Incorporated

Henrik Zetterberg

Sahlgrenska universitetssjukhuset

University College London (UCL)

Göteborgs universitet

UCL Institute of Neurology

Kaj Blennow

Gilead Sciences Incorporated

Göteborgs universitet

Magnus Gisslen

Sahlgrenska universitetssjukhuset

Göteborgs universitet

PLoS ONE

1932-6203 (ISSN)

Vol. 14 12 e0226276

Ämneskategorier

Klinisk laboratoriemedicin

Miljömedicin och yrkesmedicin

Neurologi

DOI

10.1371/journal.pone.0226276

PubMed

31826005

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Senast uppdaterat

2019-12-23