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

描述(由申请人提供)：这项研究将扩展基于艾滋病毒检测和对已确诊的艾滋病毒感染者的治疗的寻求-检测-治疗-保留(STTR)策略。总体目标是通过采取具体干预措施，减少急性(AHI)、新近(RHI)和已确诊的艾滋病毒感染者，特别是有物质使用障碍(包括酒精)患者的艾滋病毒传播危险行为的影响，从而提高STTR战略的效力。这项研究将在秘鲁利马进行，那里的药物滥用极大地促进了MSM中艾滋病毒的传播。这项建议中的新颖之处在于调查了对艾滋病毒感染不同阶段的个人进行抗逆转录病毒(ART)和酒精使用障碍的循证治疗(AUD)干预对整个社区艾滋病毒传播的影响。我们打算提供社区动员和合作伙伴服务的最佳做法，以增加接受检测的高危男男性接触者的数量(SEEK)；扩大检测算法以检测AHI、RHI和已确定的感染(TEST)；与护理和及时的抗逆转录病毒治疗(治疗)挂钩；以及促进持续的艾滋病毒护理和治疗(RESTORE)。广泛的艾滋病毒检测将使用第四代EIA检测和联合NAAT检测来检测AHI。具体目标1将通过审查男男性接触者在通过伙伴追踪和系统发育分析确定的传播群中报告使用物质(主要是酒精和可卡因)的作用，来调查吸毒和酒精使用对艾滋病毒传播的人群一级的影响。这项分析还将包括对患有AHI或RHI的男性与已确定的艾滋病毒感染对联网人群(如男男性接触者)传播的贡献进行建模。精液中的HIV病毒载量(VL)将在6个月内在患有AHI和RHI的MSM中进行测量，这些人将被随机分为立即或延迟抗逆转录病毒治疗。这些数据以及血浆VL将被用来评估ART对传染性的影响以及在此期间不坚持的潜在影响。为减少AHI或已确定感染的男性中与药物滥用相关的进一步传播而进行的联合干预的人口影响的模拟将包括以下数据：药物和酒精使用；AHI的检测频率和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留存情况；用药依从性；以及其他干预过程数据。具体目标2将重点放在酒精上，这是利马男男性接触者的“首选药物”。使用安慰剂对照试验，我们将测试缓释纳曲酮(NTX-XR)在改善HIV和酒精治疗结果方面的有效性，包括与在HIV感染的所有阶段(急性、近期和确诊)患有AUDS的MSM使用酒精相关的HIV危险行为。AIM 2的数据还将被用来模拟包括药物使用干预在内的人群水平的潜在额外好处，以减少不安全的性行为，并提高STTR干预中对ART的依从性。

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.