Does choice of combination antiretroviral therapy (cART) alter changes in cerebral function testing after 48 weeks in treatment-naive, HIV-1-infected individuals commencing cART? A randomized, controlled study.
BACKGROUND
Neurocognitive impairment remains prevalent, despite combination antiretroviral therapy (cART). Differences between changes in cerebral function and alternative cARTs have not been prospectively assessed.


METHODS
Treatment-naive, HIV-1-infected individuals randomly allocated to commence cART (tenofovir-emtricitabine plus either efavirenz [arm 1], atazanavir-ritonavir [arm 2], or zidovudine-abacavir [arm 3]) were eligible. Cerebral function tests included neurocognitive testing and assessment of cerebral metabolites using proton magnetic resonance spectroscopy in several anatomical voxels, including right frontal white matter and right basal ganglia, at baseline and after 48 weeks. N-acetylaspartate-to-creatine (NAA/Cr) ratios were calculated. Both the differences between changes in neurocognitive function and NAA/Cr ratios over 48 weeks and the study arms (arm 1 vs arm 2; arm 1 vs arm 3) were assessed.


RESULTS
Thirty subjects completed study procedures (9, 9, and 12 subjects in arms 1, 2, and 3, respectively). Mean CD4+ cell counts (+/- standard deviation) were 218 +/- 87 cells/microL at baseline and 342 +/- 145 cells/microL at week 48. The mean plasma HIV-1 RNA level was <50 copies/mL for 28 of the 30 subjects at week 48. Over 48 weeks, greater improvements in identification reaction time (P = .04) and executive function (P = .02) were observed in arm 3, compared with arm 1 (0.03, -0.30, -0.50 log10 ms change in identification reaction time, in arms 1, 2, and 3, respectively). Increases in the NAA/Cr ratio were observed in all voxels (maximum 38% in right basal ganglia), with greater increases observed in arm 1 than in arm 2 (P = .03) in frontal white matter (30%, -7%, and 0% change in the NAA/Cr ratio, in arms 1, 2, and 3, respectively).


CONCLUSIONS
To our knowledge, this is the first study to prospectively describe different changes in cerebral function testing parameters between different cARTs. Greater improvements in neuronal recovery (NAA/Cr ratio) were observed for recipients of tenofovir-emtricitabine plus efavirenz (arm 1), and greater improvements in neurocognitive function testing were observed for recipients of tenofovir-emtricitabine plus zidovudine-abacavir (arm 3).
Clinical Trials, St Mary's Hospital, Imperial College London, London, UK. a.winston@imperial.ac.uk
Alan
A
Winston
Chris
C
Duncombe
Patrick C K
PC
Li
John M
JM
Gill
Stephen J
SJ
Kerr
Rebekah
R
Puls
Kathy
K
Petoumenos
Simon D
SD
Taylor-Robinson
Sean
S
Emery
David A
DA
Cooper
D015526:AIDS Dementia Complex / Q000453:epidemiology*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001923:Brain Chemistry; D003401:Creatine / Q000032:analysis; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D009483:Neuropsychological Tests; D011446:Prospective Studies
D019380:Anti-HIV Agents; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine