ALCOHOL EFFECTS ON THYMIC IMMUNE RESPONSE TO HAART

描述（由申请人提供）：酒精使用已被证明对免疫系统有深远的影响。然而，关于酒精使用对艾滋病毒免疫功能低下个体的影响的信息是有限的和有争议的。随着高效联合治疗（HAART）的出现，HIV感染者的酒精相关研究主要集中在酒精摄入引起的行为问题，包括对治疗方案的依从性差。在艾滋病毒感染患者中，依从性低于95%与病毒载量反弹、有限的免疫反应和耐药性有关。因此，如果艾滋病毒感染者要最大限度地从抗逆转录病毒疗法中获益，严格遵守药物治疗至关重要。特别令人感兴趣的是一种平行现象，表明尽管依从性良好，但一些个体没有表现出强大的免疫和/或病毒学反应。已经确定了几个因素，包括患者的年龄和开始HAART时的CD4消耗水平。我们的初步数据表明，“大量饮酒”也可能影响HAART治疗的有效性和实现CD4显著增加的能力。拟议的少数派新研究者申请将评估“重度饮酒”（男性每周214杯，女性每周700杯）对艾滋病毒/艾滋病患者免疫功能（胸腺补充）和抗逆转录病毒治疗反应（CD4、病毒载量和精神状态）的影响。在这项纵向研究中，将招募115名艾滋病毒阳性的“重度酒精使用者”和115名艾滋病毒阳性的“非酒精使用者”，并进行为期6个月的随访。使用标准问卷，将获得详细的社会人口统计、医疗、酒精使用和艾滋病毒药物和依从性历史。酒精对HAART有效性的影响将通过比较胸腺大小、比例和产生初始细胞CD4+ CD45RA+CD62L+（胸腺产生）、CD8、病毒载量和精神状态在基线和随时间的变化进行研究。我们假设酒精对胸腺的影响可能不仅影响基于抗逆转录病毒的免疫补充，还影响与hiv相关的认知改变，因此可能影响HAART的治疗效果。我们的长期目标是扩大与艾滋病毒患病期间饮酒有关的生物医学知识，并提供生物医学信息，以便为艾滋病毒感染者，特别是酗酒者制定治疗战略。

DESCRIPTION (provided by applicant): Alcohol use has been shown to have a profound effect on the immune system. Information regarding the impact of alcohol use on HIV immunocompromised individuals, however, is limited and controversial. With the advent of highly active combination therapy (HAART), alcohol related research in HIV infected subjects has mainly focused on the behavioral problems caused by alcohol intake including poor adherence to therapeutic regimens. In HIV infected patients, adherence levels below 95% have been associated with viral load rebound, limited immune response and drug resistance. Strict adherence to medication, is therefore critical if HIV infected patients are to benefit maximally from HAART. Of particular interest is a parallel phenomenon, showing that despite good adherence, some individuals do not demonstrate a robust immune and/or virological response. Several factors have been identified and include age of the patient and level of CD4 depletion at the time of HAART initiation. Our preliminary data indicate that "heavy alcohol use" may also influence the effectiveness of HAART treatment and ability to achieve a significant CD4 increase. The proposed Minority New Investigator application will evaluate the impact of "heavy alcohol use" (214-drinks/per week for men, >7drinks/per week in women) on immune function (thymus repletion) and response to antiretroviral treatment (CD4, viral load and mental status) in HIV/AIDS. In this longitudinal study, 115 HIV+ "heavy alcohol users" and 115 HIV+ "non-alcohol users" will be enrolled and followed over a 6-month period. Using standard questionnaires, a detailed sociodemographic, medical, alcohol use and HIV medication and adherence history will be obtained. The impact of alcohol on the effectiveness of HAART will be investigating by comparing thymus size, proportion and production naive cells CD4+ CD45RA+CD62L+ (thymic production), CD8, viral load and mental status at baseline and over time. We hypothesize that alcohol induced effects on the thymus may influence not only antiretroviral-based immune repletion, but also HIV-related cognitive alterations and may, therefore, affect the therapeutic benefits of HAART. Our long-term objectives are to extend biomedical knowledge related to alcohol use during HIV disease and provide biomedical information to develop therapeutic strategies for HIV infected subjects, particularly those who are also alcohol abusers.