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) 无法完全根除 HIV。需要能够消除持久性病毒宿主或增强宿主免疫力以防止病毒在停止 ART 后从这些宿主中反弹的策略；一种可能性是治疗性疫苗接种。我们报告了一项随机、安慰剂对照试验的结果，该试验在 HIV 感染早期开始接受 ART 且免疫系统预计相对完整的患者中进行了治疗性疫苗方案。我们研究的目的是确定疫苗是否安全以及是否可以诱导免疫反应，从而在停止 ART 后维持血浆病毒血症的抑制。⁺ T 细胞反应，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 细胞隔室中 HIV 储库的大小没有影响。值得注意的是，安慰剂组 26% 的受试者在治疗中断后表现出持续抑制病毒血症（<400 拷贝/毫升），自发抑制率高于先前报道的。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未来试验旨在实现无 ART 控制 HIV 感染的干预措施的设计具有潜在的重要意义。