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CEREBRAL FUNCTION PARAMETERS IN PEOPLE LIVING WITH HIV SWITCHING INTEGRASE INHIBITOR
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Results: Of 202 PLWH, median (IQR) age 55 (48, 60) years, 152 (75%) male, 136 (67%) black, median recent CD4+ T cell count 576 (401, 818) cells/mm3, 96% HIV RNA <200 copies/ml, 99 (49%) were on INSTI-based ART (40.4% raltegravir, 29.3% elvitegravir, 30.3% dolutegravir), while 103 (51%) were on non-INSTI based ART.
A composite volumetric measurement for learning/memory brain regions was significantly smaller in the INSTI group compared to non INSTI group (figure b). Functional connectivity was reduced in the memory resting state network in the INSTI group compared to the non-INSTI group (figure c).
Conclusion: We demonstrated worse learning/memory neuropsychological performance; smaller volumetric measurement in regions associated with learning/memory and decreased functional connections in the resting state memory network in those on INSTI-based regimens. Our results suggest a dysfunction in the learning/memory network but prospective studies are required to explore this further.
CROI/2019: Memory and Learning Dysfunction with Integrase Strand Transfer Inhibitor Use
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CEREBRAL FUNCTION PARAMETERS IN PEOPLE LIVING WITH HIV SWITCHING INTEGRASE INHIBITOR
Reported by Jules Levin
CROI 2019
Borja Mora-Peris1, Laura Else2, Jaime Vera-Rojas3, Caire Petersen1, Maryam Khan1, Sujan Dilly Penchala2, Sofia Toniolo3, Mara Cercignani3, Michael R. Keegan4, Saye Khoo2, Alan Winston1
1Imperial College London, London, UK,2University of Liverpool, Liverpool, UK,3Brighton and Sussex Medical School, Brighton, UK,4ViiV Healthcare, London, UK
Abstract
Different antiretroviral therapy (ART) agents and combinations may have differing effects on cerebral function. We assessed detailed changes in cerebral function parameters in people-living-with HIV (PLWH) on ART switching integrase inhibitor.
Neurologically asymptomatic PLWH on tenofovir-DF/emtricitabine plus raltegravir 400mg twice daily with plasma HIV RNA <20 copies/mL for at least 3 months were randomly allocated on a 1:2 basis to remain on raltegravir (Arm1) or to switch to dolutegravir 50 mg once daily (Arm2) for 120 days. Changes in several cerebral function parameters were assessed which included cognitive function (reported as a z-score composite of 7 domains), patient-reported outcome measures (PROMs; PHQ-9 and Beck's depression questionnaires), cerebrospinal fluid (CSF) parameters (CSF HIV RNA, tryptophan and phenylalanine metabolites, neopterin, ART exposure and an in-vitro CSF antiretroviral infectivity assay using astrocyte derived cell cultures) and cerebral magnetic resonance (MR) imaging (proton spectroscopy (H1-MRS) in three anatomical locations). CSF infectivity models are expressed as half-maximal inhibitory concentration scores (-log2IMIC50) and ART concentrations were measured by HPLC–tandem mass spectrometry with geometric means (GMs) and 95% CIs calculated.
Of 20 subjects completing study procedures, 19 were male, 14 were of white ethnicity, median age (IQR) was 43 (11.5) years and mean (SD) baseline CD4+count was 717 (298) cells/μL. No treatment related adverse events were observed and plasma HIV RNA remained <20 copies/mL in all. Over 120 days, no statistically significant differences in changes in overall cognitive performance, PROMs, CSF tryptophan metabolite ratios, CSF antiretroviral activity scores or cerebral metabolite ratios were observed (table 1). A small difference was observed in CSF neopterin concentration between treatment arms (table 1). CSF HIV RNA was <5 copies/mL at day 120 in all subjects. GM CSF dolutegravir concentration assessed pre-dose was 7.6 ng/mL (95% CI: 5.2-11.1).
In this comprehensive assessment of cerebral function parameters in virologically suppressed PLWH switching integrase inhibitor, we observed no significant changes in clinical, CSF biomarker or cerebral imaging parameters.
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