Gender Differences In HIV-1 Pathogenesis

描述（由申请人提供）：虽然HIV-1发病机制的性别差异证据越来越多，但仍然很少有研究直接比较HIV感染男性和女性的免疫和病毒学参数。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研究感染艾滋病毒的男性，使研究人员和临床医生将从男性身上吸取的经验教训推断到感染艾滋病毒的女性人数不断增加。事实上，艾滋病毒流行病是一种男女皆患的疾病，异性传染和妇女感染的比率正在上升。

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.