Bansal Anju, Sterrett Sarah, Erdmann Nathan, Westfall Andrew O, Dionne-Odom Jodie, Overton Edgar T, Goepfert Paul A
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
AIDS. 2015 Nov;29(17):2245-54. doi: 10.1097/QAD.0000000000000860.
HIV elite controllers suppress HIV viremia without antiretroviral therapy (ART), yet previous studies demonstrated that elite controllers maintain an activated T-cell phenotype. Chronic immune activation has detrimental consequences and thus ART has been advocated for all elite controllers. However, elite controllers are not a clinically homogenous group. Since CD4% is among the best predictors of AIDS-related events, in the current study, we assessed whether this marker can be used to stratify elite controllers needing ART.
Sixteen elite controllers were divided into two groups based on CD4% (EC > 40% and EC ≤40%), and T-cell subsets were analyzed for markers of memory/differentiation (CD45RA, CCR7, CD28), activation (CD38/HLA-DR), immunosenescence (CD57), costimulation (CD73, CD28) and exhaustion (PD-1, CD160, Tim-3). Monocyte subsets (CD14, CD16) were also analyzed and sCD14 levels were quantified using ELISA.
In the EC group, expression of activation, exhaustion, and immunosensescence markers on T cells were significantly reduced compared with the EC group and similar to the seronegative controls. The EC group expressed higher levels of costimulatory molecules CD28 and CD73 and had lower levels of monocyte activation (HLA-DR expression) with a reduced frequency of inflammatory monocyte (CD14 CD16) subset. Furthermore, the EC group maintained a stable CD4% during a median follow-up of 6 years.
Elite controllers with preserved CD4T cells (EC) have normal T-cell and monocyte phenotypes and therefore may have limited benefit from ART. CD4% can be an important marker for evaluating future studies aimed at determining the need for ART in this group of individuals.
HIV精英控制者在无抗逆转录病毒治疗（ART）的情况下可抑制HIV病毒血症，但先前的研究表明，精英控制者维持着活化的T细胞表型。慢性免疫激活具有有害后果，因此一直主张对所有精英控制者进行ART治疗。然而，精英控制者并非临床同质群体。由于CD4%是艾滋病相关事件的最佳预测指标之一，在本研究中，我们评估了该标志物是否可用于对需要ART的精英控制者进行分层。
16名精英控制者根据CD4%分为两组（EC>40%和EC≤40%），分析T细胞亚群的记忆/分化标志物（CD45RA、CCR7、CD28）、活化标志物（CD38/HLA-DR）、免疫衰老标志物（CD57）、共刺激标志物（CD73、CD28）和耗竭标志物（PD-1、CD160、Tim-3）。还分析了单核细胞亚群（CD14、CD16），并使用ELISA定量sCD14水平。
与EC≤40%组相比，EC>40%组T细胞上的活化、耗竭和免疫衰老标志物表达显著降低，与血清阴性对照组相似。EC>40%组共刺激分子CD28和CD73表达水平较高，单核细胞活化水平（HLA-DR表达）较低，炎症单核细胞（CD14+CD16+）亚群频率降低。此外，在中位随访6年期间，EC>40%组的CD4%保持稳定。
CD4+T细胞保存良好的精英控制者（EC>40%）具有正常的T细胞和单核细胞表型，因此可能从ART中获益有限。CD4%可能是评估未来旨在确定该组个体是否需要ART的研究的重要标志物。
