Despite substantial clinical benefits, complete eradication of HIV has not been possible using antiretroviral therapy (ART) alone. Strategies that can either eliminate persistent viral reservoirs or boost host immunity to prevent rebound of virus from these reservoirs after discontinuation of ART are needed; one possibility is therapeutic vaccination. We report the results of a randomized, placebo-controlled trial of a therapeutic vaccine regimen in patients in whom ART was initiated during the early stage of HIV infection and whose immune system was anticipated to be relatively intact. The objectives of our study were to determine whether the vaccine was safe and could induce an immune response that would maintain suppression of plasma viremia after discontinuation of ART. Vaccinations were well tolerated with no serious adverse events but produced only modest augmentation of existing HIV-specific CD4⁺ T cell responses, with little augmentation of CD8⁺ T cell responses. Compared with placebo, the vaccination regimen had no significant effect on the kinetics or magnitude of viral rebound after interruption of ART and no impact on the size of the HIV reservoir in the CD4⁺ T cell compartment. Notably, 26% of subjects in the placebo arm exhibited sustained suppression of viremia (<400 copies/ml) after treatment interruption, a rate of spontaneous suppression higher than previously reported. Our findings regarding the degree and kinetics of plasma viral rebound after ART interruption have potentially important implications for the design of future trials testing interventions aimed at achieving ART-free control of HIV infection.

尽管有显着的临床益处，但仅使用抗逆转录病毒疗法（ART）尚不可能完全根除艾滋病毒。需要采取消除持久性病毒储存库或增强宿主免疫力以防止停止抗逆转录病毒治疗后病毒从这些储存库反弹的策略；一种可能性是治疗性疫苗接种。我们报告了一项治疗性疫苗方案的随机、安慰剂对照试验的结果，试验对象是在 HIV 感染早期就开始接受 ART 治疗且免疫系统预计相对完整的患者。我们研究的目的是确定疫苗是否安全，是否可以诱导免疫反应，从而在停止 ART 后维持对血浆病毒血症的抑制。疫苗的耐受性良好，没有出现严重的不良事件，但仅对现有的 HIV 特异性 CD4 ⁺ T 细胞反应产生适度增强，而对 CD8 ⁺ T 细胞反应几乎没有增强。与安慰剂相比，疫苗接种方案对 ART 中断后病毒反弹的动力学或幅度没有显着影响，并且对 CD4 ⁺ T 细胞室中 HIV 储存库的大小没有影响。值得注意的是，安慰剂组中有 26% 的受试者在治疗中断后表现出病毒血症的持续抑制（<400 拷贝/ml），自发抑制率高于之前报道的水平。我们关于 ART 中断后血浆病毒反弹的程度和动力学的研究结果对于未来旨在实现无 ART 控制 HIV 感染的试验干预措施的设计具有潜在的重要意义。