University of California-San Diego, San Diego, California, USA.
Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Clin Infect Dis. 2023 Sep 18;77(6):866-874. doi: 10.1093/cid/ciad265.
Neurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system.
A5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with dolutegravir (DTG) + MVC, DTG + Placebo, or Dual - Placebo in PWH with plasma HIV RNA <50 copies/mL on ART and NCI. The primary outcome was the change on the normalized total z score (ie, the mean of individual NC test z scores) at week 48.
Of 357 screened, 191 enrolled: 71% male, 51% Black race, 22% Hispanic ethnicity; mean age 52 years; mean CD4+ T-cells 681 cells/µL. Most (65%) had symptomatic HIV-associated NC disorder. Study drug was discontinued due to an adverse event in 15 (8%) and did not differ between arms (P = .17). Total z score, depressive symptoms, and daily functioning improved over time in all arms with no significant differences between them at week 48 or later. Adjusting for age, sex, race, study site, efavirenz use, or baseline z score did not alter the results. Body mass index modestly increased over 96 weeks (mean increase 0.32 kg/m2, P = .006) and did not differ between arms (P > .10).
This is the largest, randomized, placebo-controlled trial of ART intensification for NCI in PWH. The findings do not support empiric ART intensification as a treatment for NCI in PWH on suppressive ART. They also do not support that DTG adversely affects cognition, mood, or weight.
接受抗逆转录病毒疗法（ART）的艾滋病毒（HIV）感染者（PWH）中神经认知障碍（NCI）很常见，并且可能是由于 HIV 在中枢神经系统中持续复制所致。
A5324 是一项随机、双盲、安慰剂对照的 96 周临床试验，研究了在接受 ART 且血浆 HIV RNA<50 拷贝/ml 且有 NCI 的 PWH 中，强化 ART 治疗（使用多替拉韦[DTG] + 米替福新[MVC]、DTG + 安慰剂或双重安慰剂）的效果。主要结局是在第 48 周时，标准化总 Z 评分的变化（即个体 NC 测试 Z 评分的平均值）。
在 357 名筛选者中，有 191 名入组：71%为男性，51%为黑人，22%为西班牙裔；平均年龄 52 岁；平均 CD4+T 细胞 681 个/µL。大多数（65%）有症状性 HIV 相关的 NCI 障碍。由于不良事件，15 名（8%）患者停止使用研究药物，各治疗组间无差异（P =.17）。所有组的总 Z 评分、抑郁症状和日常功能均随时间改善，在第 48 周或之后，各治疗组间无显著差异。根据年龄、性别、种族、研究地点、依非韦伦使用情况或基线 Z 评分进行调整，结果无变化。96 周内体重指数（BMI）适度增加（平均增加 0.32kg/m2，P =.006），各治疗组间无差异（P>.10）。
这是最大的、随机的、安慰剂对照的强化 ART 治疗 NCI 的临床试验。结果不支持在接受抑制性 ART 的 PWH 中，经验性强化 ART 是治疗 NCI 的方法。也不支持 DTG 会对认知、情绪或体重产生不良影响。
