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Memory and Learning Dysfunction with Integrase Strand Transfer Inhibitor Use
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Reported by Jules Levin
CROI 2019 March 4-7 Seattle
Jane A O'Halloran1, Sarah A Cooley2, Jeremy F Strain2, Robert Paul3, Rachel Presti1, Beau Ances2
1 Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States;2Department of Neurology, Washington University School of Medicine, St Louis, MO, United States 3Missouri Institute of Mental Health, University of Missouri, St Louis, MO, United States
Background: Integrase strand transfer inhibitors (INSTIs )have been associated with neuropsychiatric symptoms in postmarketing analysis. However, limited data exists on the effect of these drugs on neurocognitive function. We assessed neurocognitive function and neuroimaging in people living with HIV (PLWH) on INSTI-based regimens
Methods: We performed across-sectional analysis of PLWH on ART aged>18 years. PLWH with < eight years of education or a history of confounding neurological disorders were excluded. A battery of neuropsychologica ltests were used to calculate global decit scores (GDS) in the domains of learning/memory, executive function, motor/psychomotor speed and total GDS. Structural brain volumes and resting stated functional connectivity were obtained using magnetic resonance imaging on the same day as neurocognitive testing. Comparisons made using parametric or non-parametric analyses as appropriate.
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. No between group difference was identified in age, sex, race, education, smoking status, depression scores, psychiatric medication use, HIV infection duration or nadir and recent CD4+ T cell count. On neuropsychological assessment, PLWH in the INSTI group had worse learning/memory domain scores compared with those on non-INSTI based ART (1.25 (0.25, 2) versus 0.25 (0 ,1.8); p=0.02) (figure a). This remained significant when corrected for nadir CD4+ T cell count, current ART regimen duration, current NNRTI or PI use, current psychiatric medication use or having previously received another ART regimen (p=0.04). 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.
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