French-British Hospital Institute, Levallois-Perret, France.
APHP Hospital Ambroise Paré, Versailles Saint Quentin en Yvelines University, Boulogne, France.
J Antimicrob Chemother. 2021 Feb 11;76(3):743-752. doi: 10.1093/jac/dkaa473.
Despite the effectiveness of antiretroviral (ARV) therapy to control HIV infection, HIV-associated neurocognitive disorders (HAND) remain frequent. The Neuro+3 study assessed the cognitive improvement associated with ARV intensification based on increased CNS penetration effectiveness (CPE) scoring ≥+3 and total CPE score ≥9.
Thirty-one patients, aged 18-65 years, with confirmed diagnosis of HAND and effective ARV therapy were included. The cognitive improvement was measured using Frascati three-stage classification and global deficit score (GDS) after 48 and 96 weeks of ARV intensification. Ultrasensitive HIV-RNA, neopterin, soluble CD14, CCL2, CXCL10, IL6, IL8 and NF-L were measured in plasma and cerebrospinal fluid at Day 0 (baseline), Week 48 (W48) and W96.
The intensified ARV was associated with a median (IQR) CPE score increase from 6 (4-7) at baseline to 10 (9-11). From baseline to W96, the median (IQR) GDS decreased from 1.4 (0.8-2.2) to 1.0 (0.6-2.0) (P = 0.009); HAND classification improved from 2 to 1 HIV-associated dementia, 22 to 8 mild neurocognitive disorders, 7 to 17 asymptomatic neurocognitive impairment and 0 to 5 patients without any neurocognitive alterations (P = 0.001). In multivariable linear regression analysis, GDS improvement at W96 was significantly associated with CPE score ≥9 after intensification (P = 0.014), CD4 lymphocyte increase at W48 (P < 0.001) and plasma CXCL10 decrease at W96 (P = 0.001).
In patients with HAND, a significant cognitive improvement was observed after the ARV intensification strategy, with a higher CPE score. Cognitive improvement was more often observed in the case of a switch of two drug classes, arguing for better control of CNS HIV immune activation.
尽管抗逆转录病毒 (ARV) 疗法可有效控制 HIV 感染，但仍频繁出现与 HIV 相关的神经认知障碍 (HAND)。Neuro+3 研究评估了基于 CNS 穿透效果 (CPE) 评分增加≥+3 和总 CPE 评分≥9 的 ARV 强化治疗与认知改善的相关性。
31 名年龄在 18-65 岁之间、确诊为 HAND 且 ARV 治疗有效的患者被纳入研究。采用 Frascati 三阶段分类和总体缺陷评分 (GDS) 在 ARV 强化治疗后 48 周和 96 周评估认知改善。在第 0 天（基线）、第 48 周（W48）和第 96 周（W96）时，在血浆和脑脊液中测量超敏 HIV-RNA、新蝶呤、可溶性 CD14、CCL2、CXCL10、IL6、IL8 和 NF-L。
强化 ARV 治疗后，CPE 评分中位数（IQR）从基线时的 6（4-7）增加到 10（9-11）。从基线到 W96，GDS 中位数（IQR）从 1.4（0.8-2.2）降至 1.0（0.6-2.0）（P=0.009）；HAND 分类从 2 例艾滋病相关痴呆、22 例轻度神经认知障碍、7 例无症状神经认知障碍和 0 例无任何神经认知改变改善至 1 例（P=0.001）。多变量线性回归分析显示，W96 时 GDS 改善与强化治疗后 CPE 评分≥9（P=0.014）、W48 时 CD4 淋巴细胞增加（P<0.001）和 W96 时血浆 CXCL10 降低（P=0.001）显著相关。
在 HAND 患者中，采用 ARV 强化治疗策略后观察到显著的认知改善，CPE 评分较高。在两种药物类别转换的情况下，更常观察到认知改善，这表明更好地控制了中枢神经系统 HIV 免疫激活。
