LYMPHATIC TISSUE SAMPLING TO QUANTITATE TISSUE ASSOCIATED HIV 1

在最近使用核苷类似物和蛋白酶抑制剂组合的第三阶段研究中，大多数受试者通过RNA测定判断为无菌，在一些系列中通过培养判断。我们小组使用AZT/3TC和奈非那韦的组合，在12周内在11名受试者中实现了这一点。同样，在我们的研究中，几乎所有接受AZT/3TC和利托那韦或吲地那韦治疗的新感染艾滋病毒的受试者，根据病毒RNA检测和PBMC共培养确定，这两种有效的艾滋病毒-1蛋白水解酶抑制剂都已变为抗病毒药。然而，长期的无氧血症的意义仍不清楚。这项研究将包括对艾滋病毒感染者的淋巴组织进行采样，这些人在接受治疗后至少有九个月的无菌血症。其目的是提供额外的诊断标准，这可能有助于确定可能被建议停止治疗的受试者。如果在淋巴组织中没有发现活跃的病毒复制的证据，这将表明长期的无氧血症是“病毒衰竭”的征兆。淋巴组织将接受病毒培养以及聚合酶链式反应和原位聚合酶链式反应技术，以评估是否存在活跃的病毒复制。这一关键数据对于回答HIV-1感染能否在人类宿主中治愈的问题至关重要。

In recent Phase-III studies using combinations of nucleoside analogues and protease inhibitors, most subjects were rendered aviremic as judged by RNA determinations and in some series by culture. Our group, using a combination of AZT/3TC and nelfinavir, has achieved this in 11/11 subjects in 12 weeks. Similarly, in our studies nearly all newly HIV-infected subjects treated with AZT/3TC and either ritonavir or indinavir, both potent bioavailable inhibitors of HIV-1 protease have become aviremic as determined by viral RNA determination and PBMC co-culture. However, the significance of prolonged aviremia remains unclear. This study will involve sampling lymphatic tissue of HIV-infected subjects who as a result of treatment have had a period of at least nine months of aviremia. The goal is to provide additional diagnostic criteria, which may be useful to identify subjects that may be advised to discontinue treatment . If no evidence of active viral replication in lymphatic tissue were to be found it would suggest that prolonged aviremia is indicative of "viral burnout." Lymphatic tissue will be subjected to viral culture as well as PCR and in-situ PCR techniques to assess for the presence of active viral replication. This critical data is essential to answer the question whether HIV-1 infection can be cured in a human host.