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III期研究中，通过RNA测定和在一些系列中通过培养判断，大多数受试者呈现了禽流感。 我们的小组，使用AZT/3 TC和奈非那韦的组合，在12周内在11/11的受试者中实现了这一目标。 同样，在我们的研究中，几乎所有接受AZT/3 TC和利托那韦或茚地那韦治疗的新感染HIV的受试者，通过病毒RNA测定和PBMC共培养确定，这两种HIV-1蛋白酶的有效生物可利用抑制剂都已成为aviremic。 然而，长期无病毒血症的意义仍不清楚。 这项研究将涉及对HIV感染受试者的淋巴组织进行采样，这些受试者由于治疗而具有至少9个月的病毒血症期。 目的是提供额外的诊断标准，这可能有助于识别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病毒复制的证据，则表明长期的病毒血症是“病毒衰竭”的指示。“淋巴组织将接受病毒培养以及PCR和原位PCR技术，以评估是否存在活跃的病毒复制。 这些关键数据对于回答HIV-1感染是否可以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.