Acute HIV infection - A key link for transmission prevention

描述(由申请人提供)： 艾滋病毒急性感染者(AHI)可能是艾滋病毒感染继续传播的主要原因，尤其是在撒哈拉以南非洲。AHI是从感染到血清转换之间的时间，持续时间长达10-12周。在这一短暂的时间窗口内，病毒迅速复制，导致血液和生殖器分泌物中艾滋病毒RNA浓度较高。因此，在无保护措施的性交过程中传播的可能性非常高。识别AHI患者并进行干预以减少继续传播是预防艾滋病毒的一个诱人但未经证实的机会。我们提出了一项积极的艾滋病毒传播预防计划，以识别AHI患者，并从行为和生物上进行干预。我们的中心假设是，急性艾滋病毒感染者在艾滋病毒传播中发挥着重要作用。我们进一步假设，对急性感染者的行为和治疗干预将减少进一步的传播。为了解决这些假设，我们将进行一项探索性研究，并辅之以数学建模，以评估拟议的预防计划的潜在影响。我们建议的研究的具体目标是：1)制定一项新的计划，通过识别马拉维利隆圭的急性艾滋病毒感染者(AHI)并向其提供信息来预防艾滋病毒的传播；2)评估短期的联合行为和抗逆转录病毒疗法(ART)干预措施，以防止AHI患者中的艾滋病毒传播；3)使用数学模型确定干预措施的每个组成部分的潜在个人和联合影响。为了实现这些目标，我们将利用我们在马拉维利隆圭的成熟基础设施。我们将利用新的和现有的技术来更快地识别AHI患者。确诊后，患者将立即随机接受标准咨询、强化行为干预或行为干预结合短期抗逆转录病毒治疗(ART)。行为干预以信息-动机-行为技能模型为基础。ART将使用新的有效抗逆转录病毒药物来快速阻止艾滋病毒复制并限制传染性。利用在这项试点研究中收集的数据，我们将使用严格的数学建模来评估预防计划对社区内疫情的潜在影响，并计划进行一项大型随机试验。急性艾滋病毒感染者(AHI)是艾滋病毒感染的最早阶段，可能以很高的速度传播艾滋病毒感染，特别是在撒哈拉以南非洲地区。鉴于这种重要的可能性，我们假设，对急性感染者的行为和治疗干预将减少它们的传播。为了解决这一假设，我们将进行一项探索性研究，结合数学模型，检查行为干预与抗逆转录病毒治疗疗程相结合对AHI患者的潜在影响。

DESCRIPTION (provided by applicant): Persons with acute HIV infection (AHI) may be responsible for a substantial proportion of onward transmission of HIV infection, especially in sub-Saharan Africa. AHI, the period between infection and seroconversion, lasts up to 10-12 weeks. During this brief window of time, the virus replicates rapidly, leading to high concentrations of HIV RNA in blood and genital secretions. Consequently, the probability of transmission during unprotected intercourse is very high. Identifying persons with AHI and intervening to reduce onward transmission represents a tantalizing, but unproven, opportunity for HIV prevention. We propose an aggressive HIV transmission prevention program to identify persons with AHI and intervene behaviorally and biologically. Our central hypothesis is that persons with acute HIV infection play an important role in HIV transmission. We further hypothesize that behavioral and treatment interventions in acutely infected persons will reduce onward transmission. To address these hypotheses, we will conduct an exploratory study complemented by mathematical modeling to assess the potential impact of the proposed prevention program. The specific aims of our proposed study are to: 1) Develop a novel program to prevent HIV transmission by identifying and informing persons with acute HIV infection (AHI) in Lilongwe, Malawi, 2) Evaluate a short-term, combined behavioral and antiretroviral therapy (ART) intervention to prevent HIV transmission among persons with AHI, 3) Determine the potential individual and combined impact of each component of the intervention using mathematical modeling. To achieve these aims, we will use our well-established infrastructure in Lilongwe, Malawi. We will take advantage of new and existing technologies to identify people with AHI more rapidly. Immediately after diagnosis, persons will be randomized to standard counseling, an intensive behavioral intervention, or the behavioral intervention combined with short term antiretroviral therapy (ART). The behavioral intervention is based on the Information-Motivation- Behavioral Skills Model. The ART will use new and potent antiretroviral drugs to rapidly block HIV replication and limit infectiousness. Using the data collected in this pilot study, we will use rigorous mathematical modeling to assess the potential impact of the prevention program on the epidemic within a community and plan a large randomized trial. Persons with acute HIV infection (AHI), the earliest stage of HIV infection, may transmit HIV infection at a high rate, especially in sub-Saharan Africa. Given this important possibility, we hypothesize that behavioral and treatment interventions in acutely infected persons will reduce their transmission. To address this hypothesis, we will conduct an exploratory study, coupled with mathematical modeling, to examine the potential impact of combining a behavioral intervention with a course of antiretroviral treatment in persons with AHI.