Tang Bin, Ellis Ronald J, Vaida Florin, Umlauf Anya, Franklin Donald R, Dastgheyb Raha, Rubin Leah H, Riggs Patricia K, Iudicello Jennifer E, Clifford David B, Moore David J, Heaton Robert K, Letendre Scott L
Department of Psychiatry, University of California San Diego, San Diego, CA 92093, USA.
Department of Neurosciences, University of California San Diego, San Diego, CA 92093, USA.
Brain Commun. 2024 Jul 29;6(4):fcae224. doi: 10.1093/braincomms/fcae224. eCollection 2024.
Neuropsychiatric complications such as neurocognitive impairment and depression are common in people with HIV despite viral suppression on antiretroviral therapy, but these conditions are heterogeneous in their clinical presentations and associated disability. Identifying novel biopsychosocial phenotypes that account for neurocognitive performance and depressive and functional symptoms will better reflect the complexities encountered in clinical practice and may have pathological and therapeutic implications. We classified 1580 people with HIV based on 17 features, including 7 cognitive domains, 4 subscales of the Beck depression inventory-II, 5 components of the patient's assessment of own functioning inventory, and dependence in instrumental and basic activities of daily living. A two-stage clustering procedure consisting of dimension reduction with self-organizing maps and Mahalanobis distance-based -means clustering algorithms was applied to cross-sectional data. Baseline demographic and clinical characteristics were compared between the phenotypes, and their prediction on the biopsychosocial phenotypes was evaluated using multinomial logistic regression. Four distinct phenotypes were identified. Participants in Phenotype 1 overall did well in all domains. Phenotype 2 had mild-to-moderate depressive symptoms and the most substance use disorders. Phenotype 3 had mild-to-moderate cognitive impairment, moderate depressive symptoms, and the worst daily functioning; they also had the highest proportion of females and non-HIV conditions that could affect cognition. Phenotype 4 had mild-to-moderate cognitive impairment but with relatively good mood, and daily functioning. Multivariable analysis showed that demographic characteristics, medical conditions, lifetime cocaine use disorder, triglycerides, and non-antiretroviral therapy medications were important variables associated with biopsychosocial phenotype. We found complex, multidimensional biopsychosocial profiles in people with HIV that were associated with different risk patterns. Future longitudinal work should determine the stability of these phenotypes, assess factors that influence transitions from one phenotype to another, and characterize their biological associations.
尽管接受抗逆转录病毒治疗后病毒得到抑制，但神经精神并发症如神经认知障碍和抑郁症在艾滋病毒感染者中很常见，不过这些病症在临床表现和相关残疾方面存在异质性。识别能够解释神经认知表现以及抑郁和功能症状的新型生物心理社会表型，将能更好地反映临床实践中遇到的复杂性，并且可能具有病理学和治疗学意义。我们根据17项特征对1580名艾滋病毒感染者进行了分类，这些特征包括7个认知领域、贝克抑郁量表-II的4个分量表、患者自我功能评估量表的5个组成部分以及工具性日常生活活动和基本日常生活活动中的依赖情况。将由自组织映射进行降维和基于马氏距离的均值聚类算法组成的两阶段聚类程序应用于横断面数据。比较了各表型之间的基线人口统计学和临床特征，并使用多项逻辑回归评估它们对生物心理社会表型的预测。识别出了四种不同的表型。表型1的参与者在所有领域总体表现良好。表型2有轻度至中度抑郁症状且物质使用障碍最多。表型3有轻度至中度认知障碍、中度抑郁症状且日常功能最差；他们中女性以及可能影响认知的非艾滋病毒病症的比例也最高。表型4有轻度至中度认知障碍，但情绪和日常功能相对较好。多变量分析表明，人口统计学特征、医疗状况、终生可卡因使用障碍、甘油三酯和非抗逆转录病毒治疗药物是与生物心理社会表型相关联的重要变量。我们在艾滋病毒感染者中发现了与不同风险模式相关的复杂、多维度的生物心理社会概况。未来的纵向研究应确定这些表型的稳定性，评估影响从一种表型转变为另一种表型的因素，并描述它们的生物学关联。
