Liver Disease and Drug Use in the HAART Era

描述（由申请人提供）：肝脏疾病已成为HAART时代hiv感染者发病和死亡的主要原因之一，主要是由于慢性乙型和丙型肝炎感染。在过去的几年里，娱乐性毒品的使用也有所增加，它也会影响肝脏。由于缺乏评估肝脏疾病的非侵入性方法，评估和了解艾滋病毒感染者的肝脏疾病一直具有挑战性。最近，Mehta博士及其同事证实免疫球蛋白G对嗜异性α -gal表位反应的糖基化随着肝病的进展而增加。这种糖基化导致与焦点结合凝集素Aleuria aurantia （AAL）的结合增加。该建议的假设是病毒性肝炎肝相关疾病通过HAART得到改善，并受到药物使用的影响。在本提案中，AAL反应性将被用作肝脏疾病的标志物。这一假设将通过以下两个目的进行检验，使用来自多中心艾滋病队列研究（MACS）的参与者。第一个目标是一个横断面，将在开始HAART之前利用样本。本目的目的是确定合并感染HIV和乙型或丙型肝炎的患者与单独感染HIV或病毒性肝炎的患者相比，AAL反应性是否更高。由于已知HIV会加剧肝脏疾病的进展，预计在合并感染组中AAL反应性会更高。第二个目标是前瞻性的，将在目标1的样本测试后3年和6年跟踪目标1个体的AAL反应。AAL反应性随时间的变化将在每个个体中确定，并根据HIV/肝炎和HAART状态进行比较。此外，药物使用和其他协变量对AAL反应性的影响将被建模。如果用HAART控制HIV可以改善肝炎相关的肝脏疾病，我们可以预期同时感染的受试者接受HAART治疗后AAL反应性会随着时间的推移而降低。这种改善可能会因药物使用而改变，因为娱乐性药物可能具有肝毒性。了解HAART时代的肝脏疾病和娱乐性药物使用的影响对于确定hiv -病毒性肝炎合并感染个体的最佳治疗非常重要。在HAART时代，肝病已成为艾滋病毒感染者发病和死亡的主要原因之一，主要来自慢性乙型和丙型肝炎感染。本研究的主要目的是使用一种新的血清标记物（特定IgG分子的糖基化）来确定HAART在hiv -病毒性肝炎合并感染的MACS参与者中肝脏疾病分期的变化。这些信息将有助于优化艾滋病毒病毒性肝炎合并感染者的治疗。

DESCRIPTION (provided by applicant): Liver disease has emerged as one of the leading causes of morbidity and mortality of HIV-infected individuals in the HAART era, which is primarily due to chronic hepatitis B and C infections. Recreational drug use has also increased over the past few years, and it can affect the liver as well. It has been challenging to evaluate and understand liver disease in HIV-infected persons due to the lack of non-invasive methods to evaluate liver disease. Recently, Dr. Mehta and colleagues demonstrated that glycosylation of immunoglobulin G reactive to the heterophilic alpha-gal epitope increases with advancing liver disease. This glycosylation leads to increased binding to a fucose binding lectin, Aleuria aurantia (AAL). The hypothesis of this proposal is that viral hepatitis liver- related disease is improved with HAART and is affected by drug use. In this proposal, AAL reactivity will be used as a marker of liver disease. This hypothesis will be tested through the following two Aims using participants from the Multicenter AIDS Cohort Study (MACS). The first Aim is a cross-sectional and will utilize samples prior to initiation of HAART. This Aim is designed to determine if AAL reactivity is higher in persons co- infected with HIV and hepatitis B or C compared to persons with either HIV or viral hepatitis alone, or none of these infections. AAL reactivity is expected to be higher in the co-infected group since HIV is known to exacerbate liver disease progression. The second Aim is prospective and will follow AAL reactivity in the individuals in Aim 1 at 3 and 6 years after the sample tested in Aim 1. The change in AAL reactivity over time will be determined in each individual and compared based on the HIV/hepatitis and HAART status. In addition, the effect of drug use and other covariates on AAL reactivity will be modeled. If control of HIV with HAART improves hepatitis-related liver disease, we would expect that the co-infected subjects on HAART would have decreased AAL reactivity over time. This improvement could be modified by drug use since recreational drugs can be hepatotoxic. Understanding liver disease and the effects of recreational drug use in the HAART era is important for determining optimal treatment of HIV-viral hepatitis co-infected individuals. Liver disease has emerged as one of the leading causes of morbidity and mortality of HIV-infected individuals during the HAART era and is primarily from chronic hepatitis B and C infections. The chief purpose of this investigation is use a novel serum marker (glycosylation of a particular IgG molecule) to determine change in liver disease stage prospectively with HAART in HIV-viral hepatitis co-infected MACS participants. Such information will help to optimize treatment of HIV-viral hepatitis co-infected individuals.