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

随着HIV感染进展为AIDS，患者血液中的CD4 T细胞会耗尽，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，但免疫系统的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个月内，恢复的免疫系统的调节问题可能导致与分枝杆菌感染（例如：结核病）、CMV视网膜炎、B型肝炎病毒或丙型肝炎病毒相关的疾病。我们将这些疾病定义为免疫恢复性疾病（IRD），并表明它们发生在从低基线CD 4 T细胞计数开始开始HAART的四分之一的个体中。随着非洲和亚洲患者从低CD 4 T细胞计数开始开始治疗，IRD可能变得普遍。也有新的证据表明，失调的T细胞反应可能会导致疾病的免疫重建过程中的后期。例如，一些检测不到HIV的患者在HAART治疗多个月后会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的患者接受最佳治疗的艾滋病毒感染。我们将分析开始HAART的患者中CD4 T细胞计数较低的患者和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。将采集血样，用于测量已知参与不同类型免疫应答的免疫信使（细胞因子）。结果将与临床结局相关。

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.