Estimating the impact of acute-stage HIV transmission among drug users

描述(由申请人提供)：急性艾滋病毒感染(AHI)发生在个人接触并感染艾滋病毒后不久。尽管与可能持续数年或数十年的慢性感染相比，这一时期被认为是较短的(最多持续5个月)，但已证明AHI患者的传染性要强得多。这一早期阶段对吸毒者总事件感染的贡献尚不清楚。尽管以前的研究已经给出了对血清不一致夫妇和男男性行为人群这一数值的估计比例，但所有研究都只专注于通过性接触传播，而没有评估由其他方式引起的感染事件，如共用注射器。为了解决这一知识差距，该项目将首次评估AHI在包括注射吸毒者(PWID)在内的吸毒人群中传播艾滋病毒的作用。AHI在艾滋病毒总体传播中的作用对于理解正在进行的预防战略的局限性至关重要，特别是那些需要对个人进行诊断的战略。一种这样的预防战略是治疗即预防(TasP)，它通常涉及对艾滋病毒阳性者进行频繁检测和早期治疗，并使用抗逆转录病毒药物来降低他们的传染性。由于绝大多数AHI病例没有得到诊断，预防策略应该根据这一早期阶段在造成新感染方面所起的作用来提供信息，以便那些无法避免在未诊断的个体之间传播的预防方法，如TasP，得到能够避免的预防方法(例如，针头和注射器方案、暴露前预防、阿片类药物替代疗法)。 为了估计由AHI引起的新感染的比例，这项研究将使用基于代理的建模方法，该方法将跟踪“代理”虚拟人群中的传播事件，并使用先前收集的经验数据进行校准。该模型将使用纽约市大都会统计局现有的监测和观察性研究数据进行参数化，该地区拥有世界上一些最丰富的艾滋病毒经验数据。拟议的基于代理人的模型(ABM)将纳入关于吸毒人群(注射和非注射)危险行为和网络结构的经验数据，以估计在给定时间段内新感染艾滋病毒的总人数，以及在AHI期间传播导致的感染比例。作为次要目标，ABM还将用于评估在有关AHI特征(如传染性和持续时间)的不同假设下TasP策略的有效性；这将使研究人员和政策制定者了解这一前景光明的预防模式的潜在局限性。

DESCRIPTION (provided by applicant): Acute HIV Infection (AHI) occurs shortly after an individual is exposed to and infected with HIV. Although this period is believed to be short (at most 5 months in duration) compared to chronic infection, which can last for years or decades, those with AHI have been shown to be much more infectious. The contribution of this early stage to total incident infections among drug users is not known. Although previous studies have presented estimates for this value, as a proportion, for populations of serodiscordant couples and men who have sex with men, all have focused only on transmission from sexual exposures, and have not assessed incident infections arising from other modes, such as syringe sharing. To address this knowledge gap, this project will be the first to estimate the role of AHI in transmission of HIV among drug-using populations, including people who inject drugs (PWID). The role of AHI in overall transmission of HIV is crucial in understanding the limitations of ongoing prevention strategies, particularly those that require an individual to be diagnosed. One such prevention strategy is treatment as prevention (TasP), which typically involves frequent testing and early treatment of HIV positives with antiretrovirals to decrease their infectiousness. Since the vast majority of AHI cases go undiagnosed, prevention strategies should be informed by the role this early stage has in creating new infections, so that prevention modalities which are unable to avert transmission among undiagnosed individuals, such as TasP, are supplemented by those that can (e.g., needle and syringe programs, pre-exposure prophylaxis, opioid substitution therapy). In order to estimate the proportion of new infections resulting from AHI, this study will use an agent-based modeling approach that will track transmission events within a virtual population of "agents," calibrated with previously collected empirical data. The model will be parameterized using surveillance and observational study data available for the New York City Metropolitan Statistical Area, which has some of the richest HIV empirical data in the world. The proposed agent-based model (ABM) will incorporate empirical data on the risk-behaviors and network structure of drug-using populations (both injection and non-injection) to estimate both the total number of new HIV infections in a given time period, and the proportion of those infections resulting from transmission during AHI. As a secondary aim, the ABM will also be used to estimate the effectiveness of TasP strategies under different sets of assumptions regarding characteristics of AHI (such as infectiousness and duration); this will allow researchers and policy makers to understand the potential limitations of this promising prevention modality.