Whaley Kevin J, Mayer Kenneth H
Mapp Biopharmaceutical, San Diego, California.
The Fenway Institute, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
J Infect Dis. 2014 Dec 15;210 Suppl 3(Suppl 3):S674-80. doi: 10.1093/infdis/jiu398.
Human immunodeficiency virus (HIV) may be transmitted through either cell-free virions or leukocytes harboring intracellular HIV in bodily fluids. In recent years, the early initiation of combination antiretroviral therapy leading to virological suppression has resulted in decreased HIV transmission to uninfected partners. Additionally, the efficacy of primary chemoprophylaxis with oral or topical antiretroviral regimens containing tenofovir (with or without emtricitabine) has been demonstrated. However, the efficacy of these approaches may be compromised by suboptimal adherence, decreased drug concentrations in mucosal compartments in women, and genital inflammation. Furthermore, in vitro studies on the effects of tenofovir on cell-associated HIV transmission have produced conflicting results. Preclinical studies suggest that combination preventive approaches may be most effective in stopping the transmission of HIV after mucosal exposure. Since the development of antibodies were found to correlate with protection in the only effective HIV vaccine trial, the administration of preformed mucosal and systemic antibodies may inform the development of safe and effective antibody-based oral, topical, and/or systemic preexposure prophylaxis agents and provide guidance in the development of HIV vaccines that effectively block cell-associated HIV transmission.
人类免疫缺陷病毒(HIV)可通过体液中的游离病毒颗粒或携带细胞内HIV的白细胞传播。近年来,早期启动联合抗逆转录病毒疗法导致病毒学抑制,从而减少了HIV向未感染伴侣的传播。此外,含替诺福韦(有或无恩曲他滨)的口服或局部抗逆转录病毒方案进行一级化学预防的疗效已得到证实。然而,这些方法的疗效可能会因依从性欠佳、女性黏膜部位药物浓度降低以及生殖器炎症而受到影响。此外,关于替诺福韦对细胞相关HIV传播影响的体外研究结果相互矛盾。临床前研究表明,联合预防方法在黏膜暴露后阻止HIV传播方面可能最为有效。由于在唯一一项有效的HIV疫苗试验中发现抗体的产生与保护作用相关,因此给予预先形成的黏膜和全身抗体可能会为安全有效的基于抗体的口服、局部和/或全身暴露前预防药物的开发提供信息,并为有效阻断细胞相关HIV传播的HIV疫苗的开发提供指导。