Neuroradiology Department, Pitié-Salpêtrière University Hospital, APHP, Paris, France.
Infectiology Department, Garches University Hospital, Garches, France; UMR 1179, UVSQ-Paris-Saclay University, France.
J Neurol Sci. 2022 Nov 15;442:120446. doi: 10.1016/j.jns.2022.120446. Epub 2022 Oct 3.
Thirty to 50% of HIV-infected patients develop HIV-Associated Neurocognitive Disorders (HAND) despite virological control. The previously published Neuro+3 study showed their neurocognitive status can be improved by intensifying antiviral therapy. Our study is a part of the Neuro3+ study and aims to study apparent diffusion coefficient (ADC) as a biomarker for neurological improvement.
We prospectively included 31 patients with HAND. They received therapy with better CNS Penetration Effectiveness (CPE) score with two-year follow-up. Cognitive status was assessed at day 0 (D0) and week 96 (W96) using Frascati 3-stage classification and Global Deficit Score (GDS). Brain MRI at D0 and W96 assessed morphological data (white matter hyperintensities, opportunistic infections, ischemic lesions, atrophy) and measured whole brain apparent diffusion coefficient (ADC). We compared their data with a control group of 20 healthy patients with similar ages and sex ratio.
After ARV intensification, cognitive status was significantly improved: GDS (n = 1,4 vs 1,0 p = 0.01) and Frascati scale (2HAD/22MND/7ANI vs 1HAD/8MND/17ANI p = 0.001). Mean ADC was significantly higher in patients at inclusion than in controls (0.88 × 10 mm/s ± 0.06 vs 0.81 × 10 mm/s ± 0.04, p = 0.0001). ADC decreased after treatment (0.88 × 10 mm/s ± 0.06 vs 0.85 × 10 mm/s ± 0.06 (p = 0,04). In subgroup analysis, ADC significantly decreased in clinically improved patients (0.89 × 10 mm/s ± 0.07 vs 0.85 × 10 mm/s ± 0.07 (p = 0,03)) and did not significantly change in non-clinically improved patients (0.86 × 10 mm/s ± 0.07 vs 0.84 × 10 mm/s ± 0.07 (p = 0,31)). After treatment, there was no significant difference between patients and controls (0.85 × 10 mm/s ± 0.06 vs 0.81 × 10 mm/s ± 0.04, p = 0.17).
Whole-brain ADC is a good biomarker of HIV-associated neurocognitive disorders. It is significantly increased in patients with HAND compared with controls and significantly decreases after treatment. It is all the more important to have a quantitative biomarker as conventional imaging does not contribute to the diagnosis.
尽管病毒学得到控制，仍有 30%至 50%的 HIV 感染患者会出现 HIV 相关神经认知障碍（HAND）。先前发表的 Neuro+3 研究表明，通过强化抗病毒治疗可以改善他们的神经认知状态。我们的研究是 Neuro3+研究的一部分，旨在研究表观扩散系数（ADC）作为神经改善的生物标志物。
我们前瞻性纳入了 31 名 HAND 患者。他们在接受具有更好中枢神经系统穿透效能（CPE）评分的治疗后，进行为期两年的随访。在第 0 天（D0）和第 96 周（W96）使用 Frascati 3 阶段分类和全球缺陷评分（GDS）评估认知状态。脑 MRI 在 D0 和 W96 评估形态数据（白质高信号、机会性感染、缺血性病变、萎缩）和测量全脑表观扩散系数（ADC）。我们将他们的数据与 20 名年龄和性别比例相似的健康对照患者进行了比较。
在强化 ARV 治疗后，认知状态显著改善：GDS（n=14 对 10，p=0.01）和 Frascati 量表（2HAD/22MND/7ANI 对 1HAD/8MND/17ANI，p=0.001）。与对照组相比，患者的平均 ADC 在纳入时明显更高（0.88×10mm/s±0.06 对 0.81×10mm/s±0.04，p=0.0001）。治疗后 ADC 降低（0.88×10mm/s±0.06 对 0.85×10mm/s±0.06，p=0.04）。在亚组分析中，临床改善的患者 ADC 明显降低（0.89×10mm/s±0.07 对 0.85×10mm/s±0.07，p=0.03），而非临床改善的患者 ADC 无明显变化（0.86×10mm/s±0.07 对 0.84×10mm/s±0.07，p=0.31）。治疗后，患者与对照组之间无显著差异（0.85×10mm/s±0.06 对 0.81×10mm/s±0.04，p=0.17）。
全脑 ADC 是 HIV 相关神经认知障碍的良好生物标志物。与对照组相比，HAND 患者的 ADC 明显升高，治疗后明显降低。由于常规影像学对诊断没有帮助，因此有一个定量的生物标志物就更为重要。
