Treatment of HIV infection with either antiretroviral (ARV) therapy or neutralizing monoclonal antibodies (NAbs) leads to a reduction in HIV plasma virus. Both ARVs and NAbs prevent new rounds of viral infection, but NAbs may have the additional capacity to accelerate the loss of virus-infected cells through Fc gamma receptor (FcγR)-mediated effector functions, which should affect the kinetics of plasma-virus decline. Here, we formally test the role of effector function in vivo by comparing the rate and timing of plasma-virus clearance in response to a single-dose treatment with either unmodified NAb or those with either reduced or augmented Fc function. When infused into viremic simian HIV (SHIV)-infected rhesus macaques, there was a 21% difference in slope of plasma-virus decline between NAb and NAb with reduced Fc function. NAb engineered to increase FcγRIII binding and improve antibody-dependent cellular cytotoxicity (ADCC) in vitro resulted in arming of effector cells in vivo, yet led to viral-decay kinetics similar to NAbs with reduced Fc function. These studies show that the predominant mechanism of antiviral activity of HIV NAbs is through inhibition of viral entry, but that Fc function can contribute to the overall antiviral activity, making them distinct from standard ARVs.

用抗逆转录病毒（ARV）疗法或中和性单克隆抗体（NAbs）治疗HIV感染可减少HIV血浆病毒。ARV和NAb均可阻止新一轮的病毒感染，但NAb可能具有通过Fcγ受体（FcγR）介导的效应子功能加速病毒感染细胞损失的额外能力，这应影响血浆病毒下降的动力学。在这里，我们通过比较未修饰NAb或Fc功能降低或增强的单药治疗血浆病毒清除率和清除时间，正式测试了体内效应器功能的作用。当注入感染了猿猴HIV（SHIV）的恒河猴时，NAb和具有降低Fc功能的NAb之间血浆病毒下降的斜率差异为21％。经过改造的NAb在体外可增强FcγRIII的结合并改善抗体依赖性细胞的细胞毒性（ADCC），导致体内效应细胞的武装，但其导致的病毒衰减动力学类似于具有降低Fc功能的NAb。这些研究表明，HIV NAbs的主要抗病毒活性机制是通过抑制病毒进入，但Fc功能可以促进总体抗病毒活性，使其不同于标准ARV。