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Induction of Potent Anti-HIV Immune Responses In Vivo: Application to Immune Therapy for HIV
D Weiner
Univ of Pennsylvania Sch of Med., Philadelphia
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Background: Numerous studies reported CNS damage due to HIV prior to anti-retroviral therapy (ART). Our was to determine the effects of HIV on the brain of subjects on ART
Methods: 71 HIV+ subjects (44 (8yrs, log viral load = 8.89 (2.38, Sqrt CD4 = 18.55 ( 5.36, CDC Class: 39% A, 20% B, 14% on no medication, 25% on 1–2 ART medications, 61% on 3 or more ART medications) and 75 controls (41 (9yrs) were studied with: 1) structural MRI, to measure volumes of gray matter (GM) and white matter (WM) and to quantify shape differences between brain structures; 2) MR perfusion, yielding olute blood flow measurements in lobar GM and WM; 3) MR spectroscopic imaging (MRSI), for choline (Cho, a measure of inflammation) concentrations in GM and WM in each lobe; 4) neuropsychological (NP) testing, yielding summary scores in major cognitive domains; and 5) EEG-event related potentials (ERP), to measure P3a, P3b, and CNV amplitude and latencies.
Results: HIV+ participants had significantly (p < 0.05): 1) lower GM volumes throughout the brain, and contractions of tissue in GM, WM and thalamus and CSF expansions detected by deformation morphometry; 2) lower frontal GM blood flow; 3) higher parietal WM Cho; 4) impaired working memory, processing speed, and global cognition; 5) prolonged latency of the auditory and visual P3b, reduced amplitude of auditory P3b and late phase of the contingent negative variation (CNV). Preliminary longitudinal studies on 32 HIV+ and 16 HIV– participants (mean scan interval 26 mos) show progressive brain tissue loss and cognitive deterioration.
Conclusions: HIV+ subjects on “effective” ART have widespread GM volume loss, WM contractions, parietal WM inflammation, and impaired cognition as measured by NP testing and ERPs. Preliminary longitudinal results suggest that HIV mediated brain injury is an ongoing process despite ART.
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