Omole Tosin E, Nguyen Huong Mai, Marcinow Agata, Oo Myo Minn, Jahan Naima, Ssemaganda Aloysious, Severini Giulia, Thomas Katherine K, Celum Connie, Mugo Nelly, Mujugira Andrew, Kublin James, Corey Lawrence, Sivro Aida, Lingappa Jairam R, Gray Glenda, McKinnon Lyle R
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
Department of Global Health.
J Infect Dis. 2025 Apr 15;231(4):e770-e780. doi: 10.1093/infdis/jiae638.
CD4+ T cells expressing α4β7 are optimal targets for human immunodeficiency virus (HIV) infections, with higher pre-HIV α4β7hi expression linked to increased HIV acquisition and progression in South African women. However, similar associations were not observed in men who have sex with men or people who inject drugs in the Americas, indicating need for further research.
This retrospective case-control study enrolled heterosexual men and women from South Africa (HIV Vaccine Trials Network [HVTN] 503) and East Africa (Partners Preexposure Prophylaxis/Couples' Observational Study [PP/COS]), quantifying α4β7 expression on CD4+ T cells as a predictor of subsequent HIV risk using flow cytometry analyses.
Associations between α4β7hi expression and HIV acquisition varied across cohorts. In HVTN 503, women had a higher risk estimate compared to men, but this was not significant. In PP/COS, α4β7hi expression was generally protective, particularly in Ugandans. Additionally, α4β7hi expression inversely correlated with peak viral load in PP/COS but not in HVTN 503; in the latter cohort, α4β7hi expression was inversely correlated with the CD4/CD8 ratio and predicted rapid CD4+ T-cell decline, similar to what was observed previously in South Africa.
These findings suggest that α4β7hi expression on CD4+ T cells may not predict HIV acquisition and progression in all contexts, which may be due to cohort effects, modes of transmission, viral clade, or other factors.
表达α4β7的CD4+ T细胞是人类免疫缺陷病毒（HIV）感染的最佳靶标，在南非女性中，HIV感染前较高的α4β7高表达与HIV感染增加及病情进展相关。然而，在美洲的男男性行为者或注射吸毒者中未观察到类似关联，这表明需要进一步研究。
这项回顾性病例对照研究纳入了来自南非（HIV疫苗试验网络[HVTN] 503）和东非（伴侣暴露前预防/夫妻观察性研究[PP/COS]）的异性恋男性和女性，使用流式细胞术分析定量CD4+ T细胞上α4β7的表达，作为后续HIV感染风险的预测指标。
α4β7高表达与HIV感染之间的关联在不同队列中有所不同。在HVTN 503中，女性的风险估计高于男性，但不显著。在PP/COS中，α4β7高表达通常具有保护作用，尤其是在乌干达人中。此外，α4β7高表达与PP/COS中的病毒载量峰值呈负相关，但在HVTN 503中并非如此；在后者队列中，α4β7高表达与CD4/CD8比值呈负相关，并预测CD4+ T细胞快速下降，这与之前在南非观察到的情况类似。
这些发现表明，CD4+ T细胞上的α4β7高表达可能并非在所有情况下都能预测HIV感染和病情进展，这可能是由于队列效应、传播方式、病毒分支或其他因素所致。
