Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
Institut de Recerca de la SIDA irsiCaixa, Hospital Universitari 'Germans Trias i Pujol', Badalona, Universitat Autònoma de Barcelona (UAB), Catalonia, Spain.
Clin Microbiol Infect. 2015 Jan;21(1):103.e1-6. doi: 10.1016/j.cmi.2014.08.002. Epub 2014 Oct 29.
We characterized maraviroc susceptibility of dual/mixed tropic viruses from subjects enrolled onto phase IIb study A4001029. Maraviroc baseline plasma samples from 13 multidrug-experienced subjects were sequenced and the HIV-1-env gene cloned into pNL4.3Δenv to obtain recombinant viruses. The V3 region was sequenced by the Sanger method and ultradeep sequencing. By analysing subjects having a weighted optimized background therapy susceptibility (wOBT) score of <1, 3/7 subjects were characterized by good in vivo and in vitro response to maraviroc therapy. Molecular docking simulations allowed us to rationalize the maraviroc susceptibility of dual/mixed tropic viruses. A subset of subjects with dual/mixed tropic viruses responded to maraviroc. Further investigations are warranted of CCR5 antagonists in subjects carrying dual/mixed tropic virus that explore the feasible use of maraviroc in subjects that is potentially larger than those infected with a pure R5 virus.
我们对参加 A4001029 期 IIb 研究的双重/混合嗜性病毒的马拉维若治疗敏感性进行了研究。从 13 名多重耐药经验丰富的受试者中采集马拉维若基线血浆样本并进行测序，然后将 HIV-1-env 基因克隆到 pNL4.3Δenv 中以获得重组病毒。通过桑格法和超高深度测序对 V3 区进行测序。通过分析加权优化背景治疗敏感性（wOBT）评分<1 的受试者，有 3/7 名受试者对马拉维若治疗具有良好的体内和体外反应。分子对接模拟使我们能够合理化双重/混合嗜性病毒的马拉维若敏感性。具有双重/混合嗜性病毒的一部分受试者对马拉维若有反应。需要进一步研究携带双重/混合嗜性病毒的受试者中的 CCR5 拮抗剂，以探索马拉维若在可能比感染纯 R5 病毒的受试者中更广泛应用的可能性。
