IMMUNOLOGIC APPROACHES TO THE THERAPY OF HIV-1 INFECTION

人们集中精力研究 HIV患者免疫干预的治疗方面 感染 正在进行的免疫学和抗病毒研究 间歇给予白细胞介素（IL-2）和 继续使用核苷类似物。 IL-2治疗导致持续的 CD 4细胞数量增加，活化表达减少 CD 8细胞上的标志物;表现出这些免疫学 结果显示，缓解与基线CD 4计数直接相关。 在每次治疗结束时，病毒载量出现一过性和持续性增加 输注被发现。 通过IL-2阻断细胞因子诱导的尝试 在体内使用喷替福林未能产生临床益处。 一 比较IL-2加核苷类似物与 继续单独使用核苷;第二个随机对照组 一项多中心试验也在继续进行，比较3天、4天和5天 将IL-2加核苷输注至单独核苷。 的剂量 一项评估安全性和免疫活性的递增试验， 皮下施用IL-2的患者扩大到包括患有以下疾病的患者： 不太严重的疾病。 一项评估免疫和抗病毒的研究 静脉内IL-2与HIV-1抑制剂组合的活性 启动蛋白酶。 一项研究开始确定是否时机 IL-2治疗与实验室免疫活性相关， 更大和更持久的反应比施用IL-2对固定的 方案. 评价抗TNF的安全性和活性的研究 抗体和可溶性TNF受体。 一项研究比较 IL-2单独给药至IL-2与任一抗TNF抗体联合给药 或沙利度胺开始使用。 一种抗gp 120抗体，其来源于 重组文库已被鉴定并准备用于临床 发展 一项研究评估了 过继转移的、遗传标记的、同基因的淋巴细胞被 进行;含有标记基因的细胞继续在 术后28 ~ 48周， 转移 一项基因治疗研究已经开始测试 重复输注同基因的CD 8细胞， CD 4-zeta TCR受体。

An intensive effort was directed toward studying the potential therapeutic aspects of immunologic interventions in patients with HIV infection. Ongoing studies evaluating the immunologic and antiviral effects of intermittent administration of interleukin (IL-2) and nucleoside analogues were continued. IL-2 therapy resulted in sustained increases in numbers of CD4 cells and decreased expression of activation markers on CD8 cells; the probability of manifesting these immunologic responses was shown to be directly associated with baseline CD4 count. Transient and consistent increases in viral load at the end of each infusion were revealed. Attempts to block cytokine induction by IL-2 with pentoxifylline in vivo failed to produce a clinical benefit. A randomized controlled trial comparing IL-2 plus nucleoside analogues to nucleosides alone was continued; a second randomized controlled multicenter trial was also continued comparing 3-, 4-, and 5-day infusions of IL-2 plus nucleosides to nucleosides alone. A dose escalation trial evaluating the safety and immunologic activity of subcutaneously administered IL-2 was expanded to include patients with less advanced disease. A study evaluating the immunologic and antiviral activity of intravenous IL-2 in combination with an inhibitor of HIV-1 protease was initiated. A study was begun to determine whether timing IL-2 therapy around laboratory correlates of immune activity produces greater and more durable responses than administering IL-2 on a fixed regimen. Studies evaluating the safety and activity of an anti-TNF antibody and a soluble TNF receptor were completed. A study comparing IL-2 administration alone to IL-2 combined with either anti-TNF antibody or thalidomide was begun. An anti-gp120 antibody derived from a recombinatorial library was identified and is being prepared for clinical development. A study evaluating the survival and distribution of adoptively transferred, genetically marked, syngeneic lymphocytes was undertaken; cells containing the marker gene continue to be detected in the peripheral blood of all 6 recipients from 28 to 48 weeks post- transfer. A gene therapy study was begun testing the safety and activity of repeated infusions of syngeneic CD8 cells engineered with a chimeric CD4 -zeta TCR receptor.