(O3) Switching to FTC/TAF from either ABC/3TC or FTC/TDF does not affect central nervous system HIV-1 infection


Aylin Yilmaz [1], Lars Hagberg [1], Åsa Mellgren [2], Dietmar Fuchs [3], Staffan Nilsson [4], Kaj Blennow [5, 6], Henrik Zetterberg [5, 6, 7, 8], Magnus Gisslén [1]


[1] Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden [2] Department of Research, Södra Älvsborg Hospital, Borås, Sweden [3] Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria [4] Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden [5] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden [6] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, Sweden [7] Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK [8] UK Dementia Research Institute at UCL, London, UK


Background: Despite suppressive antiretroviral therapy (ART), many HIV-infected individuals have low-level persistent immune activation in the central nervous system (CNS). Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and abacavir/lamivudine (ABC/3TC) have been the most widely used nucleoside analogues for several years. In 2015, when this study was initiated, a new prodrug for tenofovir, tenofovir alafenamide fumarate (TAF), was introduced. One potential concern regarding TAF and its effect in CNS is that TAF is a stronger substrate for P-glycoprotein (P-gp) vs TDF, which could theoretically decrease its CNS exposure since substrates for P-gp are subject to active blood-brain barrier efflux. Our aim was to investigate if switching from FTC/TDF or ABC/3TC to FTC/TAF would lead to changes in residual intrathecal immune activation, viral load, or neurocognitive function.

Methods: In this prospective study, we included 20 HIV-infected neuroasymptomatic adults (11 on ABC/3TC and 9 on FTC/TDF) selected from the prospective Gothenburg HIV CSF study cohort who for backward comparison recently had undergone a previous research lumbar puncture when on treatment with the same regimen as on baseline. We performed lumbar punctures, veni punctures, and neurocognitive testing at baseline and after three and 12 months. At the baseline visit all participants changed their nucleoside analogues to FTC/TAF without any other changes to the ongoing ART regimen. We analysed CSF and plasma HIV RNA, CSF neopterin, CSF beta-2-microglobulin, IgG index, albumin ratio, and CSF NFL at the pre-study visit, baseline and follow-up. Cognitive function in five domains was assessed by CogState.

Results: After three and 12 months of follow-up, there were no significant changes in CSF and plasma HIV RNA, CSF neopterin, CSF beta-2-microglobulin, IgG index, albumin ratio, CSF NFL, or neurocognitive function in any of the groups.

Conclusion: Switching to FTC/TAF from ABC/3TC or FTC/TDF was neutral on HIV CNS infection and inflammation.