Paper # 434|
cART Alters Changes in Cerebral Function Testing after 48 Weeks in Treatment-naïve, HIV-1-infected Subjects Commencing cART
A Winston1, C Duncombe2, P Li3, J Gill4, S Kerr2,5, Rebekah Puls5, K Petoumenos5, S Taylor-Robinson1, S Emery5, D Cooper5, and the Altair Study Group
1Imperial Coll London, UK; 2HIVNAT Res Collaboration, Bangkok, Thailand; 3Queen Elizabeth Hosp, Kowloon, Hong Kong; 4Calgary Regional Hlth Authority, Canada; and 5Univ of New South Wales, Sydney, Australia
Background: Neurocognitive (NC) impairment
remains prevalent, despite combination antiretroviral therapy (cART).
Differences between changes in cerebral function tests and alternative cART
have not previously been prospectively assessed.
Methods: HIV-infected therapy-naïve
individuals, randomly allocated to commence cART within the ALTAIR study
(TDF/FTC plus either EFV (arm 1), ATV/RTV (arm 2) or AZT/ABC (arm 3)) were
eligible. Cerebral function tests included computerised NC testing (CogState™)
and assessment of cerebral metabolites using cerebral proton-MRS in 3
anatomical voxels (right frontal white (FWM), grey matter and basal ganglia
(RBG)) at baseline and after 48 weeks on study. N-acetyl-aspartate/creatine
(NAA/Cr) ratios were calculated. Differences between changes in NC function and
NAA/Cr ratios over 48 weeks and study arms (arm 1 vs 2 and 1 vs 3) were
assessed by linear regression modelling.
Results: In this study, 30 subjects completed
study procedures (9, 9, and 12 subjects in arms 1, 2, and 3, respectively).
Mean CD4+ counts (SD, cells/mL)
were 218 (87) and 342 (145) at baseline and at week 48, respectively. Plasma
HIV RNA was <50 copies/mL in 28/30 subjects at week 48. Over 48 weeks,
greater improvements in identification reaction time (IRT, P =0.04)
and executive function (P =0.02) were observed in arm 3 vs 1
(+0.03, –0.30, –0.50 log10 msec change IRT, in arms 1, 2, and 3,
respectively). Increases in NAA/Cr were observed in all voxels (maximum 38% in
RBG) over 48 weeks of study. In a multivariate model, statistically
significantly greater increases in NAA/Cr were observed in arm 1 vs 2 (P =0.03)
in FWM (30%, -7%, 0% change in NAA/Cr, in arms 1, 2, and 3, respectively).
Conclusions: This is the first study to
prospectively describe different changes in cerebral function testing parameters
between different cART. Greater improvements in neuronal recovery markers
(NAA/Cr ratio) were observed in recipients of TDF/FTC plus EFV (arm 1) and
greater improvements in NC function testing observed in recipients of TDF/FTC
plus ABC/AZT (arm 3).