Gender Differences In HIV-1 Pathogenesis

描述(申请人提供)：尽管艾滋病毒-1发病机制中性别差异的证据越来越多，但直接比较艾滋病毒感染男性和女性的免疫学和病毒学参数的研究仍然很少。美国和欧洲早期艾滋病毒流行的历史人口结构导致研究更偏向于对感染艾滋病毒的男性的研究，让研究人员和临床医生推断从男性那里学到的教训适用于越来越多的受感染的女性。事实上，艾滋病毒大流行是一种男性和女性的疾病，女性的异性传播和感染率正在上升。 从少数几项比较艾滋病毒感染男性和女性的研究中开始出现数据，这些研究表明，在艾滋病毒早期感染中，病毒载量和病毒多样性等参数存在性别差异。女性似乎在感染早期的病毒载量较低(尽管CD4+T细胞计数相似)，而病毒多样性的比率高于男性。这些差异的原因尚不清楚，但表明男性和女性在免疫病理上存在差异。 有强有力的证据表明，免疫反应调节了血浆病毒载量和病毒多样性。免疫反应的性别差异可能解释了观察到的病毒载量和多样性的差异。我们将对已知或被认为影响HIV-1感染的免疫发病机制的男性和女性的免疫参数进行系统的检查和比较。具体地说，我们建议：1.定义感染的女性和男性之间的一般免疫学差异，2.调查感染的女性和男性之间HIV-1特异性免疫反应的差异，以及3.检查特定性别的病毒多样性和差异性。 这些研究将在细胞水平上评估对感染重要的免疫学和病毒学因素。我们还将确定病毒特异性免疫反应的广度、多样性和大小，以及在感染早期检查病毒多样性。我们相信，这些研究将使我们更全面地了解艾滋病毒在女性中的发病机制，并更好地了解影响男性和女性病毒载量和多样性的机制。

DESCRIPTION (provided by applicant): While evidence of gender differences in HIV-1 pathogenesis mounts, there remain few studies that directly compare immunologic and virologic parameters in HIV infected men and women. The historical demographics of the early HIV epidemic in the United States and Europe resulted in research skewed more towards the study of HIV infected men, leaving researchers and clinicians to extrapolate the lessons learned from men to the growing numbers of infected women. For indeed, the HIV pandemic is a disease of both men and women, and rates of heterosexual transmission and infection of women are increasing. Data is beginning to emerge from the few studies that have compared HIV infected men and women that demonstrate gender differences in parameters such as viral load and viral diversity in early HIV infection. Women appear to have lower viral loads early in infection (despite similar CD4+ T-cell counts) and higher rates of viral diversity than men. The reasons for these differences are unclear but suggest immunopathologic differences between men and women. There is strong evidence that immune responses modulate both plasma viral load and viral diversity. Gender differences in immune responses might explain the observed variation in viral load and diversity. We will undertake a systematic examination and comparison of immune parameters in men and women that are known, or believed, to affect the immunopathogenesis of HIV-1 infection. Specifically we propose to: 1. Define general immunologic differences between infected women and men, 2. Investigate differences in HIV-1 specific immune responses in infected women and men, and 3. Examine gender specific viral diversity and divergence. These studies will evaluate both immunologic and virologic factors important for infection at the cellular level. We will also determine the breadth, diversity, and magnitude of virus-specific immune responses, as well as examine viral diversity early in infection. We believe that these studies will give us a more complete understanding of HIV pathogenesis in women and provide a better understanding of the mechanisms that impact viral load and diversity in both men and women.