Switching from a regimen containing abacavir/lamivudine or emtricitabine/tenofovir disoproxil fumarate to emtricitabine/tenofovir alafenamide fumarate does not affect central nervous system HIV-1 infection

Abstract

Background: Despite suppressive antiretroviral therapy (ART), many HIV-infected individuals have low-level persistent immune activation in the central nervous system (CNS). There have been concerns regarding the CNS efficacy of tenofovir alafenamide fumarate (TAF) because of its low cerebrospinal fluid (CSF) concentrations and because it is a substrate of the active efflux transporter P-glycoprotein. Our aim was to investigate whether switching from emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) or abacavir (ABC)/lamivudine (3TC) to FTC/TAF would lead to changes in residual intrathecal immune activation, viral load, or neurocognitive function.

Methods: Twenty HIV-1-infected neuro-asymptomatic adults (11 on ABC/3TC and 9 on FTC/TDF) were included in this prospective study. At baseline, all participants changed their nucleoside analogues to FTC/TAF without any other changes in their ART regimen. We performed lumbar punctures, venipunctures, and neurocognitive testing at baseline and after three and 12 months.

Results: During follow-up, there were no significant changes in CSF or plasma HIV RNA, CSF neopterin, CSF β2-microglobulin, IgG index, albumin ratio, CSF NFL, or neurocognitive function in assessed by Cogstate in any of the groups.

Conclusion: This small pilot study indicates that switching to FTC/TAF from ABC/3TC or FTC/TDF has neither a positive, nor a negative effect on the HIV infection in the CNS.

Keywords:

• HIV-1
• central nervous system
• cerebrospinal fluid
• neopterin
• NFL
• tenofovir alafenamide fumarate

Disclosure statement

HZ has served on scientific advisory boards for Eli Lilly, Roche Diagnostics, and Wave; he has received travel grants from Teva; he is also a co-founder of Brain Biomarker Solutions in Gothenburg AB, a venture-based platform company at the University of Gothenburg. KB has served as a consultant or on advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Novartis, Pfizer, and Roche Diagnostics; he is also a co-founder of Brain Biomarker Solutions in Gothenburg AB, a venture-based platform company at the University of Gothenburg. The other authors declare that they have no competing interests.

Additional information

Funding

This study was financed by grants from the Swedish State under the agreement between the Swedish government and the county councils, the ALF-agreement [ALFGBG-717531 and ALFGBG-720931], the National Institutes of Health [R01 NS094067], and Gilead Sciences [CO-SE-311-1899]. HZ is a Wallenberg Academy Fellow supported by grants from the Swedish Research Council and the European Research Council.