Differences in the direction of change of cerebral function parameters are evident over three years in HIV-infected individuals electively commencing initial cART.
BACKGROUND
Changes 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.


METHODS
Neuroasymptomatic, 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.


RESULTS
Twenty-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).


CONCLUSIONS
The 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.
Department of Medicine, Imperial College London, London, United Kingdom.
Alan
A
Winston
The Kirby Institute, University of New South Wales, Sydney NSW 2052, Australia.
Rebekah
R
Puls
The Kirby Institute, University of New South Wales, Sydney NSW 2052, Australia; HIV NAT, Bangkok, Thailand.
Stephen J
SJ
Kerr
HIV NAT, Bangkok, Thailand.
Chris
C
Duncombe
Queen Elizabeth Hospital, Hong Kong, Hong Kong.
Patrick
P
Li
Calgary Health, Alberta, Canada.
John M
JM
Gill
HIV NAT, Bangkok, Thailand.
Reshmie
R
Ramautarsing
Department of Medicine, Imperial College London, London, United Kingdom.
Simon D
SD
Taylor-Robinson
The Kirby Institute, University of New South Wales, Sydney NSW 2052, Australia.
Sean
S
Emery
The Kirby Institute, University of New South Wales, Sydney NSW 2052, Australia.
David A
DA
Cooper
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000097:blood; D001923:Brain Chemistry / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003401:Creatine / Q000097:blood; D004359:Drug Therapy, Combination / Q000009:adverse effects; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007294:Inositol / Q000097:blood
D019380:Anti-HIV Agents; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine