Association between schistosomiasis and HIV-1 acquisition, transmission and disease progression in Africa

项目摘要 据估计，全球有3550万艾滋病毒携带者和230万新感染者 随着2012年艾滋病毒的到来，需要新的具有成本效益的艾滋病毒预防方法。混合感染起着重要的作用 通过增加对艾滋病毒的易感性和增加传播，在艾滋病毒流行中发挥重要作用。血吸虫病，一种疾病 由一种寄生扁虫引起，在许多撒哈拉以南非洲国家的流行率超过20% 受艾滋病毒影响最严重的。流行病学和分子数据表明血吸虫病与艾滋病毒有关 采集和传输，但现有研究样本量小，设计横断面， 未能针对潜在的混杂因素进行调整。现有文献中的这些局限性使人们观察到 协会没有被艾滋病毒预防研究界广泛接受。我们的建议解决了这一问题 我们对艾滋病毒-1和常见的共同感染血吸虫病之间的相互作用的理解存在差距。 我们将使用从四项艾滋病毒纵向研究中收集的生物样本和数据 在肯尼亚和乌干达的血吸虫病流行地区进行传播，以解决是否 血吸虫病增加了艾滋病毒-1感染、传播或疾病进展的风险 估算与血吸虫有关的HIV感染病例的人群归因比例 感染。我们将在感染艾滋病毒前检测血吸虫感染状况，确定流行和急性感染情况 并测量生殖器分泌物和血浆中的艾滋病毒病毒载量。在目标1中，我们将估计这种关联 血吸虫感染和HIV-1感染之间的关系。我们将检验我们的假设，即血吸虫病 与感染艾滋病毒的风险增加有关。在目标2中，我们将评估 血吸虫混合感染对HIV传染性的影响。我们将检验两个假设：1)血吸虫病是 与女性和男性生殖道中艾滋病毒-1RNA水平升高有关，艾滋病毒的标志物 传播风险和2)血吸虫病与艾滋病毒传播到原发地的风险增加有关 性伴侣。在目标3中，我们将评估血吸虫合并感染是否与更快的 新感染艾滋病毒-1的人的疾病进展。我们将检验我们的假设 血吸虫病与HIV-1感染后4-12个月采集的血浆中HIV-1RNA水平升高有关 收购，这是艾滋病毒-1病毒复制增加和更严重的艾滋病毒-1疾病的衡量标准。 单剂吡喹酮可以安全地治疗血吸虫病，估计费用为美国 每次治疗0.20-0.30美元。如果我们的研究发现血吸虫病和艾滋病毒之间有很强的联系 传播、获取或疾病进展，大规模治疗的另一个好处 血吸虫病将是安全和经济有效的艾滋病毒预防方法。

PROJECT ABSTRACT With an estimated 35.5 million people living with HIV worldwide and 2.3 million people newly infected with HIV in 2012, new cost-effective HIV prevention methods are needed. Co-infections play an important role in the HIV epidemic by increasing susceptibility to HIV and increasing transmission. Schistosomiasis, a disease caused by a parasitic flatworm, has a prevalence greater than 20% in many of the sub-Saharan African countries worst impacted by HIV. Epidemiological and molecular data suggest that schistosomiasis is associated with HIV acquisition and transmission, but existing studies had small samples sizes, were cross-sectional in design, and failed to adjust for potential confounders. These limitations in the existing literature have kept the observed association from being widely accepted in the HIV prevention research community. Our proposal addresses this gap in our understanding of the interaction between HIV-1 and the common co-infection schistosomiasis. We will use biological samples and data collected from four longitudinal studies of HIV transmission conducted in schistosomiasis-endemic areas of Kenya and Uganda to address whether schistosomiasis increases the risk of HIV-1 acquisition, transmission or disease progression and estimate the population attributable fraction of HIV incident cases associated with schistosome infection. We will test schistosome infection status prior to HIV acquisition, determining both prevalent and acute infection, and measure HIV viral load in genital secretions and plasma. In aim 1, we will estimate the association between schistosome infection and HIV-1 acquisition. We will test our hypothesis that schistosomiasis is associated with an increased incidence risk of HIV acquisition. In aim 2, we will evaluate the impact of schistosome co-infection on HIV infectiousness. We will test two hypotheses: 1) that schistosomiasis is associated with increased levels of HIV-1 RNA in the genital tract of women and men, a marker of HIV transmission risk and 2) that schistosomiasis is associated with an increased risk of HIV transmission to primary sexual partners. In aim 3, we will evaluate whether schistosome co-infection is associated with more rapid disease progression among individuals newly infected with HIV-1. We will test our hypothesis that schistosomiasis is associated with increased levels of HIV-1 RNA in plasma collected 4-12 months after HIV-1 acquisition, which is a measure of increased HIV-1 viral replication and more advanced HIV-1 disease. Schistosomiasis can be safely treated with a single dose of praziquantel at an estimated cost of US $0.20-0.30 per treatment. If our study finds a strong association between schistosomiasis and HIV transmission, acquisition, or diseases progression, an additional benefit of mass treatment of schistosomiasis would be safe and cost-effective prevention of HIV.