HIV Testing and Treatment to Prevent Onward HIV Transmission among High-risk MSM

描述（由申请人提供）：这项研究将扩大寻求测试-治疗-保留（STTR）策略的基础上艾滋病毒检测和治疗的个人与建立艾滋病毒感染。总体目标是通过专门干预来提高STTR策略的有效性，以减少急性（AHI），近期（RHI）和已确定的HIV感染者，特别是那些有物质使用障碍（包括酒精）的人中HIV传播风险行为的影响。这项研究将在秘鲁的利马进行，那里的药物滥用极大地促进了艾滋病毒在男男性行为者中的传播。该提案中的新颖之处是调查在艾滋病毒感染（因此具有传染性）的各个阶段用抗逆转录病毒（ART）和酒精使用障碍（AUD）循证治疗干预个体对社区范围内艾滋病毒传播的影响。我们打算为社区动员和合作伙伴服务提供最佳实践，以增加接受检测的高危男男性行为者的数量（寻求）;扩展检测算法以检测AHI、RHI和确诊感染（检测）;与护理和及时的ART联系起来（治疗）;并促进持续的艾滋病毒护理和治疗（保留）。广泛的艾滋病毒检测将使用第四代EIA检测和合并NAAT检测来检测AHI。具体目标1将调查人口层面的影响，毒品和酒精的使用对艾滋病毒的传播，通过检查的作用，男男性接触者报告的物质使用（主要是酒精和可卡因），通过合作伙伴跟踪和系统发育分析确定的传播集群。该分析还将包括对男性AHI或RHI与已确定的HIV感染对网络人群（如MSM）传播的贡献进行建模。将在AHI和RHI的MSM中测量6个月内精液中的HIV病毒载量（VL），这些MSM将随机接受立即或延迟ART。这些数据以及血浆VL将用于估计ART对感染性的影响以及在此期间不依从的潜在影响。为减少患有AHI或已确定感染的男性中与药物滥用相关的前向传播而进行的综合干预的人群效应建模将包括以下数据：药物和酒精使用; AHI检测频率以及与护理和治疗的成功联系;性网络分析，包括药物使用的影响; ART对生殖道VL的影响;包括AHI患者在内的个人在护理中的保留;药物依从性;以及其他干预过程数据。具体目标2将侧重于酒精，这是利马男男性行为者的“首选药物”。使用安慰剂对照试验，我们将测试延长释放纳洛酮（NTX-XR）在改善HIV和酒精治疗结果方面的疗效，包括HIV风险行为，与在HIV感染的所有阶段（急性，近期和确定）与AUDs的MSM之间的酒精使用相关。目标2数据还将用于模拟在人群水平上的潜在额外益处，包括物质使用干预措施，以减少不安全性行为并提高STTR干预措施中的ART依从性。

DESCRIPTION (provided by applicant): This research will expand upon Seek-Test-Treat-Retain (STTR) strategies based on HIV testing and treatment of individuals with established HIV infection. The overall objective is to improve the efficacy of STTR strategies by specifically intervening to reduce the impact of HIV transmission risk behaviors among individuals with acute (AHI), recent (RHI) and established HIV infection, especially those with substance use disorders (including alcohol). This research will be conducted in Lima, Peru where substance misuse contributes greatly to HIV transmission among MSM. Novel within this proposal is the investigation of the impact on community- wide HIV transmission of intervening with individuals at various stages of HIV infection (and therefore infectivity) with antiretroviral (ART) and evidence-based treatments for alcohol use disorders (AUDs). We intend to provide best-practices for community mobilization and partner services to increase the number of at-risk MSM tested (seek); expansion of testing algorithms to detect AHI, RHI and established infection (test); linkage to care and timely ART (treat); and promotion of continued HIV care and treatment (retain). Widespread HIV testing will use 4th generation EIA assays and pooled NAAT testing to detect AHI. Specific Aim 1 will investigate the population-level impact of drug and alcohol use on HIV transmission by examining the role of MSM who report substance use (mostly alcohol and cocaine) in transmission clusters identified through partner tracing and phylogenetic analysis. This analysis will also include modeling of the contribution of men with AHI or RHI vs. established HIV infection to transmission among networked populations, such as MSM. HIV viral load (VL) in semen will be measured over a 6 month period in MSM with AHI and RHI who will be randomized to immediate or delayed ART. These data as well as plasma VL will be used to estimate the effect of ART on infectivity and the potential impact of non-adherence during this period. Modeling of the population effect of a combination intervention to reduce onward transmission associated with substance abuse in men with AHI or established infection will include the following data: drug and alcohol use; frequency of detection of AHI and successful linkage to care and treatment; sexual network analysis including impact of substance use; effect of ART on genital tract VL; retention of individuals, including those with AHI, in care; medication adherence; as well as other intervention process data. Specific Aim 2 will focus on alcohol, the "drug of choice" among MSM in Lima. Using a placebo-controlled trial, we will test the efficacy of extended release naltrexone (NTX-XR) in improving HIV and alcohol treatment outcomes, including HIV risk behaviors, associated with alcohol use among MSM with AUDs at all stages (acute, recent and established) of HIV infection. Aim 2 data will also be used to model the potential additional benefit on a population level of including substance-use interventions to reduce unsafe sex and improve ART adherence in STTR interventions.