Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection
Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection
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DOI：
10.1128/jvi.01340-07
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发表时间：
2007-10-01
影响因子：
5.4
通讯作者：
Markowitz, Martin
中科院分区：
文献类型：
--
作者：
Mehandru, Saurabh;Vcelar, Brigitta;Markowitz, Martin
在一项开放标签、非随机、概念验证研究中，给予了三种具有体外和体内活性的中和性单克隆抗体（MAb）2G 12、2F 5和4 E10，以尝试预防抗逆转录病毒治疗（ART）中断后的病毒反弹。入选了10名在急性和早期感染期间被确定并接受ART治疗的I型人类免疫缺陷病毒感染者。前6名患者每次输注给予3种MAb各1.0 g。其余4例患者接受2G 12 1.0 g/输注和2.0 g/输注2175和4 E10。MAb耐受性良好。观察到I级部分凝血活酶后时间缩短。在8/10例受试者中观察到病毒反弹（ART中断后28 - 73天），2/10例受试者在研究过程中保持无病毒血症。在8名病毒反弹的受试者中，有7名出现了对2G 12的明显耐药性，而血浆来源的重组病毒对2F 5和4 E10的敏感性降低既没有持续也没有持续测量。病毒反弹与胃肠道内CD 4（+）T细胞的优先消耗有关。虽然安全，单克隆抗体的使用一般延迟，但不能防止病毒反弹。应考虑进一步的试点研究与单克隆抗体的替代组合，也许额外的新的治疗方式。
Three neutralizing monoclonal antibodies (MAbs), 2G12, 2F5, and 4E10, with activity in vitro and in vivo were administered in an open-label, nonrandomized, proof-of-concept study to attempt to prevent viral rebound after interruption of antiretroviral therapy (ART). Ten human immunodeficiency virus type I-infected individuals identified and treated with ART during acute and early infection were enrolled. The first six patients were administered 1.0 g of each of the three MAbs per infusion. The remaining four patients received 2G12 at 1.0 g/infusion and 2.0 g/infusion of 2175 and 4E10. The MAbs were well tolerated. Grade I post-partial thromboplastin time prolongations were noted. Viral rebound was observed in 8/10 subjects (28 to 73 days post-ART interruption), and 2/10 subjects remained aviremic over the course of the study. In seven of eight subjects with viral rebound, clear resistance to 2G12 emerged, whereas reductions in the susceptibilities of plasma-derived recombinant viruses to 2F5 and 4E10 were neither sustained nor consistently measured. Viral rebound was associated with a preferential depletion of CD4(+) T cells within the gastrointestinal tract. Though safe, the use of MAbs generally delayed, but did not prevent, virologic rebound. Consideration should be given to further pilot studies with alternative combinations of MAbs and perhaps additional novel treatment modalities.