Schooley R T
University of Colorado Health Sciences Center, Denver, USA.
J Biol Regul Homeost Agents. 1995 Jul-Sep;9(3):110-3.
Antiretroviral chemotherapeutic agents exhibit complex immunoregulatory changes in HIV-1 infected individuals that reflect the summation of the direct effects of the agents on the immune response and indirect effects through the amelioration of viral replication. Immunological parameters are useful in the context of clinical investigation and in the management of HIV-1 infected individuals in that they serve as prognostic indicators of disease, markers of biologic activity of antiretroviral drugs, and, to a lesser extent, predictors of clinical outcome. Many questions remain in the evaluation of these parameters in the context of clinical trials and in the management of individual patients. Although it is frequently tempting to measure all available parameters in any setting, it is important to be cognizant both of cost and of the fact that many of these parameters are codependent variables (29). Most evaluations that have been undertaken to date involve nucleoside analogs, either as single agents or in combination. It is clear that CD4 cells rise in association with the initiation of non-nucleoside reverse transcriptase inhibitors and HIV-1 protease inhibitors (30-32). It is not yet clear whether the CD4 cell changes observed with these classes of drugs exhibit the same relationships with other immunologic markers or with virologic or clinical parameters. Evidence has begun to emerge that CD4 cell changes in association with HIV-1 protease inhibitor therapy may be more durable than changes in viral load as assessed by plasma HIV-1 RNA. Given the more robust antiviral potency of HIV-1 protease inhibitors alone or in combination with nucleoside analogs, it is quite likely that many of the ambiguities with respect to prior studies of immunologic markers will be resolved in that the changes observed will likely be of a much greater magnitude and duration than those seen in association with nucleoside analog monotherapy. Finally, with the advent of more potent antiviral regimens, and with the more reproducible and sensitive techniques for measuring viral replication in vivo, the cogent investigation of immunologic parameters will provide important insights into the pathogenesis of HIV-1 infection (33, 34).
抗逆转录病毒化疗药物在HIV-1感染个体中表现出复杂的免疫调节变化，这些变化反映了药物对免疫反应的直接作用以及通过改善病毒复制产生的间接作用的总和。免疫参数在临床研究以及HIV-1感染个体的管理中很有用，因为它们可作为疾病的预后指标、抗逆转录病毒药物生物活性的标志物，在较小程度上还可作为临床结局的预测指标。在临床试验背景下以及个体患者管理中评估这些参数时，仍存在许多问题。尽管在任何情况下测量所有可用参数常常很诱人，但重要的是要认识到成本问题以及许多这些参数是相互依赖变量这一事实（29）。迄今为止进行的大多数评估都涉及核苷类似物，无论是作为单一药物还是联合使用。很明显，随着非核苷逆转录酶抑制剂和HIV-1蛋白酶抑制剂的开始使用，CD4细胞数量会增加（30 - 32）。目前尚不清楚这些药物类别的使用所观察到的CD4细胞变化与其他免疫标志物或病毒学或临床参数是否呈现相同的关系。已有证据表明，与HIV-1蛋白酶抑制剂治疗相关的CD4细胞变化可能比血浆HIV-1 RNA评估的病毒载量变化更持久。鉴于HIV-1蛋白酶抑制剂单独使用或与核苷类似物联合使用时具有更强的抗病毒效力，很可能先前关于免疫标志物研究的许多模糊之处将得到解决，因为观察到的变化可能在幅度和持续时间上比核苷类似物单药治疗所见的变化大得多。最后，随着更有效的抗病毒方案的出现，以及体内测量病毒复制的更可重复和敏感的技术的出现，对免疫参数的深入研究将为HIV-1感染的发病机制提供重要见解（33, 34）。
