Riccardi Niccolò, Berruti Marco, Del Puente Filippo, Taramasso Lucia, Di Biagio Antonio
Infectious Diseases Unit, Department of Health Sciences (DISSAL), University of Genoa, Policlinico San Martino Hospital, Genoa, Italy.
Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Recent Pat Antiinfect Drug Discov. 2018;13(3):190-197. doi: 10.2174/1574891X13666181031120019.
Heavily treated HIV-1 infected patients may have limited therapeutic alternatives. In order to ensure sustained HIV-RNA suppression in these patients and to improve current antiretroviral treatment regimens in the fight against multi-drug resistant strains, new drugs are needed. Recently, two new drugs among the new generation of entry inhibitors showed promises for both their characteristics and mechanism of action.
To outline ibalizumab (Patent: US20120121597A1) and fostemsavir (Patent: US8871771) future applications in people living with multi-drug resistant HIV with few remaining treatment options.
We analysed the available literature and data from ongoing clinical trials about ibalizumab and fostemsavir.
Ibalizumab is a new humanized monoclonal antibody. It acts as post-attachment inhibitor by binding CD4 2nd domain of T lymphocyte and preventing HIV connection to CCR5 or CXCR4 and has been recently approved by Food and Drug Administration in the United States of America as a new intravenous antiretroviral agent for heavily treated HIV adults with multi -drug resistant infection. Fostemsavir (formerly BMS-663068), the oral prodrug of temsavir, is another attachment inhibitor. It acts by preventing the viral connection to CD4 by binding gp120. This drug showed encouraging results in heavily treated patients as add-on agent to current antiretroviral regimens, in particular for subtype B virus. It is currently being investigated in a phase 3, two-cohort (randomized and non-randomized), trial.
The history of ibalizumab and fostemsavir will be written in next years. Continuing the research will be crucial to obtain evidence based guidelines for the management of heavily treated HIV-1 infected patients with limited therapeutic options.
接受过大量治疗的HIV-1感染患者的治疗选择可能有限。为了确保这些患者的HIV-RNA持续受到抑制,并改进当前抗逆转录病毒治疗方案以对抗多重耐药菌株,需要新的药物。最近,新一代进入抑制剂中的两种新药因其特性和作用机制而展现出前景。
概述ibalizumab(专利:US20120121597A1)和fostemsavir(专利:US8871771)在治疗选择有限的多重耐药HIV感染者中的未来应用。
我们分析了有关ibalizumab和fostemsavir的现有文献以及正在进行的临床试验数据。
ibalizumab是一种新型人源化单克隆抗体。它通过结合T淋巴细胞的CD4第二结构域发挥附着后抑制剂的作用,阻止HIV与CCR5或CXCR4连接,最近已被美国食品药品监督管理局批准作为一种新型静脉注射抗逆转录病毒药物,用于治疗接受过大量治疗且感染多重耐药的成年HIV患者。Fostemsavir(前身为BMS-663068)是temsavir的口服前体药物,是另一种附着抑制剂。它通过结合gp120来阻止病毒与CD4连接。作为当前抗逆转录病毒方案的附加药物,该药物在接受过大量治疗的患者中显示出令人鼓舞的结果,尤其是对于B亚型病毒。目前它正在一项3期、两组(随机和非随机)试验中进行研究。
ibalizumab和fostemsavir的历史将在未来几年书写。继续开展研究对于获得基于证据的指南以管理治疗选择有限的接受过大量治疗的HIV-1感染患者至关重要。