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BRAIN VOLUMES CHANGES AFTER ABC/3TC + EFV OR TDF/FTC + ATV/r AS FIRST LINE ART
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Reported by Jules Levin
CROI 2018 March 4-7 Boston, MA
Perez-Valero I1*, Bailon L1, Gonzalez-Baeza A1, Alejos B2, Melero H3, Mapica N3, Bernardino JI1, Gonzalez-Garcia J1, Arribas JR1 on behalf of the APACHE Study Group
1Hospital Universitario La Paz, IDIPAZ, Madrid, Spain. 2. National Center of Epidemiology, Instituto de Salud Carlos III, Madrid, Spain. 3. Universidad Rey Juan Carlos, Alcorcon, Spain
From Jules: in recent few years there has been discussion about neurotoxicity of HAART & that regimens or drugs with high CNs penetration might cause neurotoxicity. While perhaps for some patients a higher CPE score might be helpful. This study compared EFV based regimen to Atazanavir based regimen and found the EFV based regimen to reduced brain volumes: the EFV regimen was associated with reduction in cortical & some sub cortical structures grey matter volumes and worse performance in speed of processing tasks.
"Our results suggest that the type of ART selected as initial therapy might have a role preserving the grey matter and the cortical integrity. The regimen with lower CP [CNS penetration] including drugs with lower in-vitro NT [neurotoxicity] tended to preserve grey matter cortical integrity than the comparator with higher CP and higher in vitro NT. Confirmatory studies are needed."
Program Abstract:
Volumetric MRI studies evaluating the effect of ART initiation over cortical and subcortical grey matter (GM) volume changes are scarce, non-randomized and don't compare the effect of ART regimens with different CNS penetration (CP) and neurotoxicity (NT) profiles.
Randomized, open-label, 24-week pilot clinical trial comparing brain structures (3T-MRI) and neurocognitive changes (NC) in 7 domains after ART initiation with arm1: ABC/3TC+EFV (higher CP and in vitro NT) vs. arm 2: TDF/FTC+ATV/r (lower CP and in vitro NT). We compared volume and thickness changes (week 24 – day 0), in patients who completed all study procedures both by intention to treat (ITT: all patients) and per protocol (PP: excluding patients who changed therapy or did not achieve virologic suppression) analysis. Volumes were calculated using Freesurfer software and normalized using the Intracranial Volume and the Mean Thickness. Comparison were performed using the Wilcoxon signed-rank test and a linear regression estimative model adjusted by significant baseline covariables. Volume changes and NC changes were correlated using Pearson's r.
25 Caucasian (91.7%) male (100%), mean age: 37.3 years, median CD4+: 480 cells and recent HIV diagnosis (mean time: 0.6 years) were included. 24 of them completed all study procedures (13 allocated to arm 1 and 11 to arm 2). No baseline differences were observed between study groups. During the study, 1 patient (arm 1) discontinued due to a non-related SAE (pneumonia) and 2 had to change therapy (EFV and ATV-related toxicities). By week 24, 10 of 12 patients on arm 1 and 9 of 10 on arm 2 achieved virologic suppression on randomized ART. At week 24, changes in total GM and cortical volumes were different between study arms, by ITT and PP (table). These volumes tended to increase in arm 2 and to decrease in arm 1. No differences were detected in subcortical GM or in cortical white matter volumes. Decrease in total cortical volume correlated (p<0.05) with lower scores in processing speed (WAIS III - Symbols Search: r=0.41), motor functioning (Grooved - Dominant Hand: r=0.48) and verbal fluency (COWAT - PMR: r=0.43).
Our results suggest that the type of ART selected as initial therapy might have a role preserving the grey matter and the cortical integrity. The regimen with lower CP including drugs with lower in-vitro NT tended to preserve grey matter cortical integrity than the comparator with higher CP and higher in vitro NT. Confirmatory studies are needed.
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