Mesquita Flavio S, Li Yijia, Li Jonathan Z
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Curr Opin HIV AIDS. 2025 Jan 1;20(1):54-60. doi: 10.1097/COH.0000000000000898. Epub 2024 Nov 7.
This review focuses on the viral and immune factors influencing HIV posttreatment control (PTC), a rare condition where individuals maintain viral suppression after discontinuing antiretroviral therapy (ART).
Studies demonstrate that early ART initiation leads to smaller HIV reservoirs and delayed viral rebound in PTCs. Virologically, PTCs harbor smaller HIV reservoirs and show lower levels of reservoir transcriptional activity compared with posttreatment noncontrollers. Immunologically, PTCs exhibit distinct T-cell dynamics, with reduced CD4+ and CD8+ T-cell activation and exhaustion, enhanced natural killer (NK) cell activity, and enhanced proliferative responses of HIV-specific CD8+ T cells post-ART interruption. Additionally, humoral immunity, particularly the development of autologous neutralizing antibodies (aNAbs), plays a role in viral control, though broadly neutralizing antibodies (bnAbs) are rare.
The mechanisms behind posttreatment control are multifactorial, involving virological and immunological factors. Early ART initiation, a smaller and less transcriptionally active HIV reservoir, and immune responses including proliferative T-cell activity and NK cell function are key contributors to achieving ART-free HIV remission.
本综述聚焦于影响HIV治疗后控制(PTC)的病毒和免疫因素,PTC是一种罕见情况,即个体在停止抗逆转录病毒治疗(ART)后仍能维持病毒抑制状态。
研究表明,早期开始ART可使PTC患者体内的HIV储存库更小,病毒反弹延迟。在病毒学方面,与治疗后未实现病毒控制者相比,PTC患者体内的HIV储存库更小,储存库转录活性水平更低。在免疫学方面,PTC患者表现出独特的T细胞动态变化,ART中断后,CD4+和CD8+T细胞的活化和耗竭减少,自然杀伤(NK)细胞活性增强,HIV特异性CD8+T细胞的增殖反应增强。此外,体液免疫,特别是自体中和抗体(aNAb)的产生,在病毒控制中发挥作用,不过广泛中和抗体(bnAb)较为罕见。
治疗后控制背后的机制是多因素的,涉及病毒学和免疫学因素。早期开始ART、HIV储存库更小且转录活性更低,以及包括增殖性T细胞活性和NK细胞功能在内的免疫反应,是实现无ART的HIV缓解的关键因素。