Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection.
Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection.
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DOI：
10.1097/psy.0000000000001129
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发表时间：
2022-10-01
影响因子：
3.3
通讯作者：
RV254/SEARCH 010 Study Team
中科院分区：
文献类型：
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作者：
Paul R;Cho K;Bolzenius J;Sacdalan C;Ndhlovu LC;Trautmann L;Krebs S;Tipsuk S;Crowell TA;Suttichom D;Colby DJ;Premeaux TA;Phanuphak N;Chan P;Kroon E;Vasan S;Hsu D;Carrico A;Valcour V;Ananworanich J;Robb ML;Ake JA;Sriplienchan S;Spudich S;RV254/SEARCH 010 Study Team
我们使用数据驱动的方法，研究了在144周的抗逆转录病毒治疗(ART)期间，在急性HIV感染(AHI)期间，CD4/CD8 T细胞比率轨迹和相关风险曲线的个体差异。共有483名AHI参与者在FieBig I-V期间开始抗逆转录病毒治疗，并完成了144周的随访评估。定义了CD_4~+、CD_8~+和CD_4/CD_8 T细胞比率轨迹，然后进行分析以确定相关的危险变量。在登记时，参与者的病毒载量(VL)中值为5.88拷贝/毫升，CD4/CD8 T细胞比率为0.71。在ART治疗144周后，CD4/CD8T细胞比率的中位数为1.3。纵向模型显示了5个CD4/CD8 T细胞比率亚组：第1组(3%)在所有就诊时表现为>；1.0；第2组(18%)和第3组(29%)在入院时表现为倒置，分别在ART后4周和12周恢复正常；第4组(31%)和5组(18%)由于CD4+T细胞恢复缓慢(第4组)或CD8+T细胞计数过高(第5组)而出现CD4/CD8T细胞比率倒置。持续性倒置对应于FieBig II后ART发作，较高的VL、可溶性CD27和TIM-3，以及较低的嗜酸性粒细胞计数。与CD8+T细胞计数高的患者相比，CD4+T细胞恢复缓慢的患者表现出更高的VL，更低的白细胞计数，更低的嗜碱性粒细胞百分比，以及标准抗逆转录病毒治疗，以及更差的心理健康和认知能力。早期HIV疾病动态预测抗逆转录病毒治疗后不良的CD4/CD8T细胞比率结果。在AHI期间，CD4+和CD8+T细胞的运动轨迹有助于逆转风险，并与特定的病毒、免疫和心理特征相对应。实现免疫正常化的辅助策略值得考虑。
We examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach. A total of 483 AHI participants began ART during Fiebig I–V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables. Participants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count. Early HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.