The current treatment for HIV-1 is based on blocking various stages in the viral replication cycle using combination antiretroviral therapy (ART). Even though ART effectively controls the infection, it is not curative, and patients must therefore continue treatment life-long.

Here we review recent literature investigating the single or combined effect of toll-like receptor (TLR) agonists and broadly neutralizing antibodies (bNAbs) with the objective to evaluate the evidence for this combination as a means towards an HIV-1 cure.

Multiple preclinical studies found significantly enhanced killing of HIV-1 infected cells by TLR agonist-induced innate immune activation or by Fc-mediated effector functions following bNAb administration. However, monotherapy with either agent did not lead to sustained HIV-1 remission in clinical trials among individuals on long-term ART. Notably, findings in non-human primates suggest that a combination of TLR agonists and bNAbs may be able to induce long-term remission after ART cessation and this approach is currently being further investigated in clinical trials.

Preclinical findings show beneficial effects of either TLR agonist or bNAb administration for enhancing the elimination of HIV-1 infected cells. Further, TLR agonist-mediated stimulation of innate effector functions in combination with bNAbs may enhance antibody-dependent cellular cytotoxicity and non-human primate studies have shown promising results for this combination strategy. Factors such as immune exhaustion, proviral bNAb sensitivity and time of intervention might impact the clinical success.

目前对 HIV-1 的治疗基于使用联合抗逆转录病毒疗法 (ART) 阻断病毒复制周期的各个阶段。尽管 ART 有效控制了感染，但它并不能治愈，因此患者必须终生接受治疗。

在这里，我们回顾了最近研究 Toll 样受体 (TLR) 激动剂和广泛中和抗体 (bNAb) 的单一或组合效应的文献，目的是评估这种组合作为治愈 HIV-1 手段的证据。

多项临床前研究发现，在施用 bNAb 后，TLR 激动剂诱导的先天免疫激活或 Fc 介导的效应子功能显着增强了对 HIV-1 感染细胞的杀伤。然而，在长期接受抗逆转录病毒疗法的个体的临床试验中，使用任一种药物的单一疗法都不会导致持续的 HIV-1 缓解。值得注意的是，在非人类灵长类动物中的发现表明，TLR 激动剂和 bNAb 的组合可能能够在 ART 停止后诱导长期缓解，目前正在临床试验中进一步研究这种方法。

临床前研究结果表明，TLR 激动剂或 bNAb 给药对增强清除 HIV-1 感染细胞的有益作用。此外，TLR 激动剂介导的先天效应器功能刺激与 bNAb 结合可能会增强抗体依赖性细胞毒性，非人类灵长类动物研究已显示这种组合策略的有希望的结果。免疫衰竭、前病毒 bNAb 敏感性和干预时间等因素可能会影响临床成功。