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。虽然与慢性感染相比，这段时间被认为很短（最多5个月），慢性感染可能持续数年或数十年，但AHI患者的传染性更强。这一早期阶段对吸毒者中总意外感染的贡献尚不清楚。虽然以前的研究对血清不一致的夫妇和男男性行为者提供了这一值的比例估计值，但所有研究都只关注性接触传播，而没有评估其他方式（如共用注射器）引起的偶发感染。为了解决这一知识缺口，该项目将首次评估AHI在吸毒人群（包括注射吸毒者）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当前预防策略的局限性至关重要，特别是那些需要个体被诊断的策略。一种这样的预防策略是治疗即预防（TasP），它通常涉及用抗逆转录病毒药物对艾滋病毒阳性者进行频繁检测和早期治疗，以降低其传染性。由于绝大多数AHI病例未得到诊断，预防策略应考虑到这一早期阶段在产生新感染方面的作用，因此，无法避免在未确诊个体中传播的预防模式，如TasP，应辅以那些可以预防的预防模式（如针头和注射器计划、暴露前预防、阿片类药物替代治疗）。

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.