Immune dysregulation in HIV patients with immune reconstitution after highly active anti-retroviral therapy

随着HIV感染发展为艾滋病，患者血液中的CD4 t细胞耗竭，剩余细胞的功能受到抑制。如果患者接受高效抗逆转录病毒疗法（HAART）治疗，一些免疫缺陷会得到解决，但免疫系统功能是否完全恢复正常仍有待确定。我们已经证明，在治疗的前6个月，恢复后的免疫系统的调节出现问题，可导致与分枝杆菌感染（如结核病）、巨细胞病毒性视网膜炎、乙型肝炎病毒或丙型肝炎病毒相关的疾病。我们将这些情况定义为免疫恢复疾病（IRD），并表明它们发生在四分之一从低基线CD4 t细胞计数开始HAART的个体中。随着非洲和亚洲患者从CD4 t细胞计数低开始治疗，IRD可能会变得普遍。也有新的证据表明，失调的t细胞反应可能在免疫重建过程的后期引起疾病。例如，一些无法检测到艾滋病毒的患者在HAART治疗数月后出现机会性感染或自身免疫性疾病。该项目将使用西澳大利亚州接受最佳治疗的艾滋病毒感染患者。我们将分析CD4 t细胞计数低且开始HAART治疗的患者和HIV感染控制良好至少6个月的患者的免疫激活和t细胞功能。血液样本将被收集用于测量已知参与不同类型免疫反应的免疫信使（细胞因子）。结果将与临床结果相关联。

As HIV infection progresses to AIDS, there is a depletion of CD4 T-cells from the patient's blood and inhibition of the function of the remaining cells. Some immune defects resolve if the patient is given treatment with highly active anti-retroviral therapy (HAART), but it remains to be determined if the function of the imune system returns fully to normal. We have shown that problems with the regulation of the restored immune system in the first 6 months of treatment can lead to diseases associated with Mycobacterial infections (eg: tuberculosis), CMV retinitis, hepatitis B virus or hepatitis C virus. We have defined these conditions as Immune Restoration diseases (IRD) and shown that they occur in one in four individuals who begin HAART from low baseline CD4 T-cell counts. IRD are likely to become common as therapy becomes available in Africa and Asia as patients begin treatment from low CD4 T-cell counts. There is also emerging evidence that dysregulated T-cell responses may cause disease later in the course of immune reconstitution. For example, some patients with undetectable HIV experience opportunistic infections or autoimmune disease after many months of HAART. This project will use West Australian patients receiving optimal therapy for their HIV infection. We will analyse immune activation and T-cell function in patients beginning HAART with low CD4 T-cell counts and patients who have had well-controlled HIV infection for at least 6 months. Blood samples will be collected for the measurement of immunological messengers (cytokines) known to be involved in different types of immune responses. The results will be correlated with the clinical outcome.