Rubin Leah H, Shirk Erin N, Pohlenz Lily, Romero Hayley, Roti Elizabeth, Dastgheyb Raha M, Santiuste Isabel, Coughlin Jennifer M, Brown Todd T, Clements Janice E, Veenhuis Rebecca T
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Infect Dis. 2025 Feb 4;231(1):165-174. doi: 10.1093/infdis/jiae460.
Monocytes are susceptible to human immunodeficiency virus (HIV) infection, form HIV reservoirs, and contribute to central nervous system complications (eg, cognitive impairment) in virally suppressed women with HIV (vsWWH). However, it remains unknown if the quality and/or quantity of the monocyte reservoir contributes to cognition in vsWWH.
Sixty-two vsWWH (mean age = 56.1 years, SD = 7.1; 93% Black, non-Hispanic; all HIV RNA <250 copies/mL) completed a cognitive test battery, blood draw, and whole-blood immunophenotyping. Monocytes and CD4 T cells were isolated from a subset of 53 participants and the HIV reservoir was assessed using cell-specific intact proviral DNA assays (IPDA). Demographically adjusted z-scores were calculated for each outcome using data from participants without HIV in the Women's Interagency HIV Study. Cognitive outcomes of interest included domain-specific and global z-scores.
Thirty-Eight percent of vsWWH had detectable intact HIV genomes in monocytes (median = 21.5 copies/million). Higher levels of intact HIV genomes per million monocytes were associated with poorer verbal memory (delayed recall, r = 0.55, P = .01; recognition, r = 0.46, P = .04), fine motor skills (r = 0.50, P = .03), and global function (r = 0.47, P = .04). Higher levels of intact HIV genomes in monocytes were associated with percent intermediate monocytes (r = 0.60, P = .008), and the ratio of intact per intermediate monocyte was associated with worse memory (r = -0.59, P = .008). There were no associations between CD4 reservoir and cognition.
The number of intact HIV genomes per million monocytes was related to poorer cognition and the percentage of intermediate monocytes. These findings suggest that the presence of HIV genomes in general do not relate to cognitive complications, but intact, and therefore potentially replication-competent HIV, may contribute to cognitive complications in vsWWH.
单核细胞易受人类免疫缺陷病毒（HIV）感染，形成HIV储存库，并导致病毒抑制的HIV感染女性（vsWWH）出现中枢神经系统并发症（如认知障碍）。然而，尚不清楚单核细胞储存库的质量和/或数量是否会影响vsWWH的认知。
62名vsWWH（平均年龄 = 56.1岁，标准差 = 7.1；93%为黑人，非西班牙裔；所有HIV RNA<250拷贝/毫升）完成了一套认知测试、血液抽取和全血免疫表型分析。从53名参与者的子集中分离出单核细胞和CD4 T细胞，并使用细胞特异性完整前病毒DNA检测（IPDA）评估HIV储存库。使用女性机构间HIV研究中未感染HIV参与者的数据，为每个结果计算人口统计学调整后的z分数。感兴趣的认知结果包括特定领域和总体z分数。
38%的vsWWH在单核细胞中可检测到完整的HIV基因组（中位数 = 21.5拷贝/百万）。每百万单核细胞中较高水平的完整HIV基因组与较差的言语记忆（延迟回忆，r = 0.55，P = 0.01；识别，r = 0.46，P = 0.04）、精细运动技能（r = 0.50，P = 0.03）和总体功能（r = 0.47，P = 0.04）相关。单核细胞中较高水平的完整HIV基因组与中间单核细胞百分比（r = 0.60，P = 0.008）相关，每个中间单核细胞的完整基因组比率与较差的记忆相关（r = -0.59，P = 0.008）。CD4储存库与认知之间无关联。
每百万单核细胞中完整HIV基因组的数量与较差的认知和中间单核细胞百分比相关。这些发现表明，一般情况下HIV基因组的存在与认知并发症无关，但完整的、因此可能具有复制能力的HIV可能导致vsWWH出现认知并发症。
