Gender Differences In HIV-1 Pathogenesis

描述（由申请人提供）：虽然HIV-1发病机制存在性别差异的证据越来越多，但仍有很少的研究直接比较HIV感染男性和女性的免疫学和病毒学参数。美国和欧洲早期艾滋病毒流行的历史人口统计数据导致研究更多地倾向于对艾滋病毒感染男性的研究，使研究人员和临床医生能够将从男性身上学到的教训外推到越来越多的感染女性身上。事实上，艾滋病毒流行病是一种男女共同的疾病，异性性传播和妇女感染的比率正在上升。 数据开始出现从少数研究比较艾滋病毒感染的男子和妇女，证明性别差异的参数，如病毒载量和病毒多样性在早期艾滋病毒感染。 女性在感染早期的病毒载量似乎较低（尽管CD 4 + T细胞计数相似），病毒多样性的比率高于男性。这些差异的原因尚不清楚，但表明男性和女性之间的免疫病理学差异。 有强有力的证据表明，免疫应答调节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变化。 我们将进行一个系统的检查和比较免疫参数的男性和女性，是已知的，或相信，影响免疫发病机制的HIV-1感染。具体而言，我们建议：1。 定义感染女性和男性之间的一般免疫学差异，2。调查感染HIV-1的女性和男性的特异性免疫反应的差异，以及3。检查性别特异性病毒多样性和分歧。 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，多样性和幅度，并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女性艾滋病毒的发病机制，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.