Differences in the Direction of Change of Cerebral Function Parameters Are Evident over Three Years in HIV-Infected Individuals Electively Commencing Initial cART

Abstract

BackgroundChanges in cerebral metabolite ratios (CMR) measured on 1H-MRS and changes in cognitive function (CF) are described in subjects commencing combination antiretroviral therapy (cART), although the dynamics of such changes are poorly understood.MethodsNeuroasymptomatic, HIV-infected subjects electively commencing cART were eligible. CMR were assessed in three anatomical voxels and CF assessed at baseline, week 48 and week 144. Overall differences in absolute change in CMRs and CF parameters between 0–48 and 48–144 weeks were assessed.ResultsTwenty-two subjects completed study procedures. Plasma HIV-RNA was <50 copies/mL in all at week 48 and in all, but two subjects at week 144. In general, between weeks 0–48 a rise in N-acetyl-aspartate(NAA)/Creatine(Cr) ratio and a decline in myo-Inositol(mI)/Cr ratio were observed. Between weeks 48–144, small rises in NAA/Cr ratio were observed in two anatomical voxels, whereas a rise in mI/Cr ratio was observed in all anatomical locations (0.31 (0.66) and -0.27 (1.35) between weeks 0–48 and 0.13 (0.91) and 1.13 (1.71) between weeks 48–144 for absolute changes in NAA/Cr and mI/Cr (SD) in frontal-grey voxel, respectively). Global CF score improved between weeks 0–48 and then declined between weeks 48–144 (0.63 (1.16) and -0.63 (0.1.41) for mean absolute change (SD) between weeks 0–48 and weeks 48–144, respectively).ConclusionsThe direction of change of cerebral function parameters differs over time in HIV-infected subjects commencing cART, highlighting the need for long-term follow-up in such studies. The changes we have observed between weeks 48–144 may represent the initial development of cerebral toxicities from cART.

White matter measures are near normal in controlled HIV infection except in those with cognitive impairment and longer HIV duration

“…This finding may reflect that ANI indeed represents a mild level of HIV brain involvement. It could also reveal that DTI FA and MD measures may not be the most sensitive to ongoing brain injury that have been shown using CSF analyses (Jessen Krut et al 2014) and 1 H-MRS (Cysique et al 2013;Winston et al 2015) in virally suppressed and ANI patients. The WM alterations were more widespread in the MND + HAD consistent with the greater severity of the underlying HIV brain involvement (major association fibers, EC, FX, and CG, for both MD and FA suggesting both atrophy and axonal injury).…”

Increased Dolutegravir Peak Concentrations in People Living With Human Immunodeficiency Virus Aged 60 and Over, and Analysis of Sleep Quality and Cognition

“…Composite scores for sleep questionnaires were calculated and interpreted as per questionnaire protocols and cutoffs (table 1). Neurocognitive scores were analysed using Cogstate® recommendations [35]. Statistical analyses were performed using Stata (version 14.1) and GraphPad Prism (version 7.03).…”

Evolution of changes in cognitive function after the initiation of antiretroviral therapy

“…Similarly, in the ALTAIR study speed and accuracy domains improved over the first year after cART initiation with no individual domain showing deterioration from baseline at week 48 [ 7 ]. However, in the long term follow up of this study a decline in global cognitive function score was observed over 144 weeks and the authors hypothesised this could be related to antiretroviral toxicities [ 12 ]. In our study, domains critically affected in HIV-associated cognitive impairment such as detection and identification times [ 13 ] deteriorated slightly at week 48 after an initial improvement at week 24 (Table 2 ).…”