HIV Superinfection after Acute and Recent Infection

项目3：重复感染或连续获得艾滋病毒变异株，可能会传播更多 抗药性的或毒性更强的。控制双重感染易感性的情况尚不清楚， 与非洲的疫情相比，B亚型疫情(如北美的疫情)可能有所不同。一个 更好地了解双重感染的风险、后果和生物决定因素将有助于指导 为感染者提供咨询，并可能为保护性免疫和艾滋病毒发病机制提供线索。 现有病例报告表明，重叠感染主要发生在最近的血清转换者中。使用 同样的检测方法，在大量已确诊的人群中没有观察到重叠感染 感染。我们现在建议将我们对双重感染的研究扩展到最近感染的人，他们 似乎有更高的风险。我们将专门测试以下假设：重复感染风险随着 艾滋病毒感染病程(Aim1a)，尽管与感染艾滋病毒-1的伴侣的接触增加(Aim1b)。我们的 研究结果表明，血清浓度，或对具有相同血清状态的伴侣的偏好，随着 感染持续时间增加。通过组合队列，提高了发现重叠感染病例的能力 在旧金山和巴西东南部。我们还将确定重叠感染或双重感染是否 与疾病进展加速有关，如血浆RNA水平、CD4T细胞计数、T细胞 细胞激活，以及朴素和记忆亚集分析(目标2)。包括具有多个基线的人员 感染有助于确保分析疾病进展的实验室标记物的能力。我们还将 研究可能决定双重感染风险的生物学机制(目标3)。我们将专门测试 假设超级感染的病毒可能具有更大的复制能力，更大的融合能力， 更广泛的趋向性，或更强的逃脱自体血清中和或细胞介导的能力 免疫反应(与项目4协调)。为了扩展我们最近的发现，我们将确定血清 随着时间的推移，中和反应变得更广泛，与重复感染风险相关。病毒式传播 表型将使用全病毒和病毒测试载体进行评估。该项目将填补以下方面的重要空白 关于双重感染和双重感染的知识，这两种感染直接关系到艾滋病毒的流行传播， 保护性免疫、二级预防和艾滋病毒发病机制。

PROJECT 3: Superinfection, or sequential acquisition of HIV variants, could spread viruses that are more drug-resistant or more virulent. The circumstances that govern susceptibility to superinfection are not known, and may differ in subtype B epidemics (like that in North America) compared with epidemics in Africa. A better understanding of superinfection risk, consequences, and biological determinants will help guide counseling of infected persons and may provide clues to protective immunity and HIV pathogenesis. Available case reports indicate that superinfection has occurred primarily in recent seroconverters. Using the same detection methods, superinfection was not observed in large cohorts of persons with established infections. We now propose to extend our research on superinfection to recently infected persons, who appear to have higher risk. We will specifically test the hypothesis that superinfection risk decreases over the course of HIV infection (aim1a) despite increases in exposure to HIV-1-infected partners (aim1b). Our findings suggest that serosorting, or preference for partners having the same serostatus, increases with increased duration of infection. The power to detect superinfection cases is enhanced by combining cohorts in San Francisco and Southeastern Brazil. We also will determine if superinfection, or dual infection, is associated with acceleration in disease progression, as indicated by plasma RNA level, CD4 T cell counts, T cell activation, and naive and memory subset analysis (aim 2). Inclusion of persons with multiple baseline infections helps assure power for analysis of laboratory markers of disease progression. We will also investigate biological mechanisms that may determine superinfection risk (aim 3). We will specifically test the hypotheses that superinfecting viruses may have greater replication capacity, greater fusion capacity, broader tropism, or increased capacity to escape from autologous serum neutralization or cell-mediated immune responses (in coordination with Project 4). To extend our recent findings, we will determine if serum neutralization responses become broader over time in a manner that correlates with superinfection risk. Viral phenotypes will be assessed using whole virus and viral test vectors. This project will fill important gaps in knowledge about superinfection and dual infection, which bear directly on the epidemic spread ofHIV, protective immunity, secondary prevention, and HIV pathogenesis.