Mitsuyasu Ronald T, Merigan Thomas C, Carr Andrew, Zack Jerome A, Winters Mark A, Workman Cassy, Bloch Mark, Lalezari Jacob, Becker Stephen, Thornton Lorna, Akil Bisher, Khanlou Homayoon, Finlayson Robert, McFarlane Robert, Smith Don E, Garsia Roger, Ma David, Law Matthew, Murray John M, von Kalle Christof, Ely Julie A, Patino Sharon M, Knop Alison E, Wong Philip, Todd Alison V, Haughton Margaret, Fuery Caroline, Macpherson Janet L, Symonds Geoff P, Evans Louise A, Pond Susan M, Cooper David A
Center for Clinical AIDS Research and Education, University of California-Los Angeles, 9911 West Pico Boulevard, Suite 980, Los Angeles, California 90035, USA.
Nat Med. 2009 Mar;15(3):285-92. doi: 10.1038/nm.1932. Epub 2009 Feb 15.
Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.
基因转移作为一种一次性治疗方法具有潜力，它可以降低病毒载量、保护免疫系统并避免终身接受高效抗逆转录病毒治疗。据我们所知，本研究是首个随机、双盲、安慰剂对照的2期细胞递送基因转移临床试验，该试验对74名感染HIV-1的成年人进行，他们接受了自体CD34+造血祖细胞递送的tat-vpr特异性抗HIV核酶（OZ1）或安慰剂。未出现与OZ1相关的不良事件。在主要终点（第47周和第48周的平均值）时，OZ1组和安慰剂组的病毒载量无统计学显著差异，但在第40 - 48周和第40 - 100周期间，OZ1组的曲线下时间加权面积显著更低。在整个100周内，OZ1组的CD4+淋巴细胞计数更高。这项研究表明，细胞递送基因转移在HIV感染者中是安全且具有生物活性的，并且可以开发为一种传统治疗产品。
