ALCOHOL EFFECTS ON THYMIC IMMUNE RESPONSE TO HAART

酒精对 HAART 胸腺免疫反应的影响

• 批准号: 6798592
• 负责人: MARIA-JOSE MIGUEZ
• 金额: $ 15.15万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6798592
• 关键词: AIDS therapy; HIV infections; alcoholic beverage consumption; alcoholism /alcohol abuse; cellular immunity; combination chemotherapy; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; helper T lymphocyte; human subject; immunosuppression; magnetic resonance imaging; patient oriented research; questionnaires; thymus; virus load; western blottings

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.

描述（由申请人提供）：酒精的使用已被证明对免疫系统有深远的影响。然而，有关饮酒对艾滋病毒免疫功能低下个体的影响的信息有限且存在争议。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上，包括对治疗方案的依从性差。在 HIV 感染患者中，低于 95% 的坚持水平与病毒载量反弹、有限的免疫反应和耐药性相关。因此，如果 HIV 感染者要从 HAART 中获得最大利益，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现象，表明尽管有良好的依从性，但一些人并未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 耗竭水平。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显着增加的能力。拟议的少数派新研究者申请将评估“重度饮酒”（男性每周饮酒 214 杯，女性每周超过 7 杯）对艾滋病毒/艾滋病免疫功能（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 HIV+“重度饮酒者”和 115 名 HIV+“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、饮酒和艾滋病药物治疗以及依从性历史。将通过比较基线和一段时间内的胸腺大小、比例和原始细胞 CD4+ CD45RA+CD62L+（胸腺生成）、CD8、病毒载量和精神状态来研究酒精对 HAART 有效性的影响。我们假设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补充，而且可能影响与 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展与艾滋病毒感染期间饮酒相关的生物医学知识，并提供生物医学信息，为艾滋病毒感染者（特别是酗酒者）制定治疗策略。

项目成果

Cognitive performance and the thymus among HIV-infected subjects receiving HAART.

• DOI: 10.2147/btt.s1753
• 发表时间: 2008-06
• 期刊: Biologics : targets & therapy
• 作者: Miguez-Burbano MJ;Lewis JE;Moreno J;Fishman J
• 通讯作者: Fishman J

The influence of different types of alcoholic beverages on disrupting highly active antiretroviral treatment (HAART) outcome.

不同类型的酒精饮料对破坏高效抗逆转录病毒治疗 (HAART) 结果的影响。

• DOI: 10.1093/alcalc/agp024
• 发表时间: 2009
• 期刊: Alcohol and alcoholism (Oxford, Oxfordshire)
• 作者: Míguez-Burbano,MaríaJosé;Lewis,JohnE;Fishman,Joel;Asthana,Deshratn;Malow,RobertM
• 通讯作者: Malow,RobertM