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者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HIV感染患者中，低于95%的依从性水平与病毒载量反弹、有限的免疫应答和耐药性有关。因此，如果艾滋病毒感染者要从HAART中最大限度地获益，严格遵守药物治疗至关重要。特别令人感兴趣的是一个平行的现象，表明尽管有良好的依从性，一些个体并没有表现出强大的免疫和/或病毒学应答。已经确定了几个因素，包括患者的年龄和HAART开始时的CD 4消耗水平。我们的初步数据表明，“重度饮酒”也可能影响HAART治疗的有效性和实现CD 4显着增加的能力。拟议的少数新研究者申请将评估“大量饮酒”（男性每周饮酒214次，女性每周饮酒> 7次）对艾滋病毒/艾滋病患者免疫功能（胸腺充盈）和抗逆转录病毒治疗反应（CD 4、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HIV+“重度酒精使用者”和115名HIV+“非酒精使用者”，并随访6个月。使用标准问卷，将获得详细的社会人口统计学、医疗、酒精使用和HIV药物和依从性史。将通过比较基线和随时间推移的胸腺大小、比例和初始细胞CD 4 + CD 45 RA + CD 62 L+（胸腺产生）、CD 8、病毒载量和精神状态，研究酒精对HAART有效性的影响。我们推测酒精对胸腺的影响不仅可能影响基于抗逆转录病毒的免疫应答，还可能影响HIV相关的认知改变，因此可能影响HAART的治疗益处。我们的长期目标是扩大与艾滋病毒疾病期间使用酒精有关的生物医学知识，并提供生物医学信息，为艾滋病毒感染者，特别是那些同时滥用酒精的人制定治疗策略。

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.