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THE USE OF LESS NEUROTOXIC ANTIRETROVIRALS: SECONDARY ENDPOINTS OF THE MARAND-X STUDY
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CROI 2021 March 6-10 Reported by Jules Levin
Andrea Calcagno1, Veronica Pirriatore1, Silvia Orlando2, Giacomo Stroffolini1, Ambra Barco1, Giulia Guastamacchia2, Giuseppe Noce3 Cristiana Atzori2, Mattia Trunfio1, Lorenzo Mighetto2, Letizia Marinaro1, Giovanni Di Perri1, Stefano Bonora1
1University of Turin, Turin, Italy, 2ASL Città di Torino, Turin,Italy, 3IRCCS SDN,Naples, Italy
Background: Despite a high prevalence (30-50%) HIV-associated neurocognitive disorders pathogenesis is incompletely understood. antiretrovirals' neurotoxicity has been suggested as a potential mechanism. Aim of the study was to measure the change in resting EEG waves, CSF biomarkers and Fibroscan measurements in PLWH with HAND randomized to a less neurotoxic regimen (darunavir/cobicistat, maraviroc, emtricitabine "MARAND") or continuing their treatment.
Methods: Adult PLWH with HAND were enrolled if presenting no major resistance-associated mutations, not on efavirenz>/darunavir, with R5-tropic HIV, without major confounding conditions, >6 months after HCV-SVR and with plasma and CSF HIV RNA <50 copies/mL. After 1:1 randomization, tests were repeated at 24 weeks: resting EEG, CSF biomarkers (HIV-RNA, tau, p-tau, Beta- amyloid1-42, S100Beta and neopterin). The freeware LORETA (low resolution brain electromagnetic tomography) was used for the estimation of EEG rhythms. Data are expressed as median (interquartile range). Non-parametric tests (Mann-Whitney and Wilcoxon's) were used.
Results: Results: In June 2020 the study was prematurely terminated for slow accrual when 38 participants were enrolled (19 per arm). Male (76.3%) and European ancestry (92.1%) were prevalent. Median age was 55 years (51-60). Plasma and CSF HIV RNA were <20 copies/mL in 33 (86.8%) and 32 (84.2%) participants; median CD4+ count was 626 cell/uL (469-772). Baseline characteristics were similar between the study arms. LORETA delta and alpha waves were similar at baseline and W24 (n=29). A significant decrease in parietal delta waves was observed in the MARAND arm (-0.69, p=0.022) but not in other waves or cortical sources. CSF HIV-RNA (n=14) was detectable in 43-44% participants at baseline and W24 with no significant difference. A significant decrease in CSF p-tau (-14.6 pg/mL, p=0.018) and an increase in CSF neopterin (+1.87 ng/mL, p=0.045) were observed in the MARAND arm. Fibroscan (n=25) stiffness and coefficient attenuation parameter (CAP) were similar at baseline and W24: we observed a significant reduction in stiffness at W24 in the MARAND arm (-0.8 KPa, p=0.038).
Conclusion: Conclusions: Despite a small sample size we observed improvement in EEG cortical sources and in hepatic stiffness in patients randomized to the experimental arm. CSF biomarkers changes (lower phosphorylated-tau and higher neopterin) need to be replicated in large cohorts.
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