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

描述（由申请人提供）：本研究将扩展基于艾滋病毒检测和治疗的寻找-测试-治疗-保留（STTR）策略。总体目标是通过具体干预减少艾滋病毒传播风险行为对急性（AHI）、近期（RHI）和已确诊艾滋病毒感染个体的影响，特别是那些有物质使用障碍（包括酒精）的个体的影响，提高STTR策略的有效性。这项研究将在秘鲁利马进行，那里的药物滥用对男男性接触者之间的艾滋病毒传播有很大影响。本提案的新颖之处在于，调查了对处于不同HIV感染阶段的个体进行抗逆转录病毒治疗（ART）和基于证据的酒精使用障碍治疗（AUDs）对社区范围内HIV传播的影响。我们打算为社区动员和伙伴服务提供最佳做法，以增加接受检测的高危男同性恋者人数（寻求）；扩展检测算法以检测AHI、RHI和确诊感染（测试）；与护理和及时抗逆转录病毒治疗（治疗）的联系；以及促进持续的艾滋病毒护理和治疗（保留）。广泛的HIV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将调查药物和酒精使用对艾滋病毒传播的人口层面影响，方法是审查报告药物使用（主要是酒精和可卡因）的男男性行为者在通过伴侣追踪和系统发育分析确定的传播集群中的作用。该分析还将包括对患有AHI或RHI的男性与已确诊的艾滋病毒感染在网络人群（如男男性接触者）中传播的贡献进行建模。将在6个月内测量患有AHI和RHI的MSM患者精液中的HIV病毒载量（VL），他们将随机接受立即或延迟抗逆转录病毒治疗。这些数据以及血浆VL将用于估计ART在此期间对传染性的影响以及不依从性的潜在影响。在患有AHI或已确诊感染的男性中，通过联合干预减少与药物滥用相关的后续传播的人群效应建模将包括以下数据：药物和酒精使用；AHI的检出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；抗逆转录病毒治疗对生殖道VL的影响保留患者，包括那些患有AHI的患者；药物治疗依从性;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“首选毒品”。通过一项安慰剂对照试验，我们将测试缓释纳曲酮（NTX-XR）在改善艾滋病毒和酒精治疗结果方面的疗效，包括艾滋病毒风险行为，这些行为与处于艾滋病毒感染各个阶段（急性、近期和已确诊）的aud男同性恋者的酒精使用有关。Aim 2的数据还将用于在人群水平上模拟包括药物使用干预措施以减少不安全性行为和提高STTR干预措施中抗逆转录病毒治疗依从性的潜在额外效益。

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.