Alcohol Misuse, Gut Microbial Dysbiosis and PrEP Care Continuum: Application and Efficacy of SBIRT Intervention

暴露前预防（PrEP），一种降低HIV阴性人群中HIV传播风险的药物方案 个人，有助于实现国家艾滋病毒预防目标。然而，临床副作用， 特别是影响胃肠道（GI）（恶心、呕吐、食欲不振）、肝脏和肾脏损伤的药物 结果可能会抑制PrEP的持久性。重要的是，酒精的使用是频繁的PrEP用户可能会相互作用 与PrEP和加剧PrEP相关的不良GI影响，从而影响PrEP的持久性。 最近的数据表明，这些副作用可能与肠道微生物组的变化有关。 （生态失调）。尽管PrEP、酒精及其联合使用可能对患者的健康产生重要影响， 肠道生态失调和随后的PrEP持续，很少有研究来阐明这种相互作用， 此外，很少有研究探讨有关酒精的决策过程 以及PrEP使用者的PrEP利用率和依从性。为了解决这些研究差距，本研究将 采用以下目标。目标1：定性研究探索酒精使用影响的机制 通过PrEP连续体的运动，并了解早期干预和治疗 方法影响酒精使用和PrEP依从性。目标2：调查SBIRT的有效性 预防危险酒精使用的干预措施及其对PrEP使用者肠道生态失调的影响。内 这项纵向队列研究，我们将确定酒精影响的参与者，使用模式 从偶发性到长期性（从事有风险或危险的使用）。目标3：确定 肠道微生物组的改变（生态失调），肠道稳态，全身性炎症，和 PrEP使用者中与危险酒精使用相关的肝病标志物。从当地招聘 PrEP诊所，我们将确定肠道微生物组，肠道稳态，全身炎症的改变 以及与酒精和PrEP使用相关的肝病标志物。我们还将进行随机对照 在PrEP使用者中进行的试验表明酒精使用增加，以测试筛查的有效性，简介 干预和转诊治疗（SBIRT）干预，以减少酒精使用，并检查随后的 与接受常规治疗的个体和未接受PrEP治疗的个体相比， 表明酒精摄入量增加最后，我们将采用定性方法（深入访谈）， 分析以了解随着时间的推移影响PrEP依从性和酒精使用的决策因素。优先 人口，包括那些从事酒精使用，需要增加参与PrEP护理 继续优化艾滋病毒预防工作。临床研究还没有集中在PrEP之间的相互作用， 酒精使用和GI不良事件。这项研究可能对减轻突出的 挑战PrEP的坚持和持久性（副作用）和阐明，从临床和公众 健康观点，促进PrEP护理连续体维持的因素。

Pre-exposure prophylaxis (PrEP), a medication regimen to reduce HIV transmission risk among HIV negative individuals, has utility in helping to reach national HIV prevention goals. However, clinical side effects, particularly those impacting gastrointestinal (GI) (nausea, vomiting, loss of appetite), hepatic and renal injury outcomes may inhibit PrEP persistence. Importantly, alcohol use which is frequent in PrEP users may interact with PrEP and exacerbate PrEP-associated adverse GI effects and consequently affect PrEP persistence. Recent data implicates that these side effects are likely associated with changes in the gut microbiome (dysbiosis). Despite the important ramifications that PrEP, alcohol, and their combined use may have on the gut dysbiosis and subsequent PrEP continuance, there is little research to elucidate this interaction and few attempts to address it. Moreover, there is little research exploring decision-making processes regarding alcohol and PrEP utilization and adherence among PrEP users. To address these gaps in research, this study will employ the following aims. Aim 1: Qualitatively explore mechanisms by which alcohol use impacts movement through the PrEP continuum and understand how an early intervention and treatment approach impacts alcohol use and PrEP adherence. Aim 2: Investigate the effectiveness of the SBIRT intervention in preventing hazardous alcohol use and its impact on gut dysbiosis in PrEP users. Within this longitudinal cohort study, we will identify alcohol impacted participants, with patterns of use ranging from episodic to long-term (engaging in risky or hazardous use). Aim 3: To determine alterations in the gut microbiome (dysbiosis), intestinal homeostasis, systemic inflammation, and markers of liver disease associated with hazardous alcohol use among PrEP users. Recruiting from local PrEP clinics, we will determine alterations in the gut microbiome, intestinal homeostasis, systemic inflammation and markers of liver disease associated with alcohol and PrEP use. We will also execute a randomized control trial among PrEP users demonstrating heightened alcohol use to test the effectiveness of the Screening, Brief Intervention, & Referral to Treatment (SBIRT) intervention to reduce alcohol use and examine subsequent impact on the gut microbiome compared to individuals receiving treatment as usual and PrEP users not demonstrating elevated alcohol use. Finally, we will employ qualitative methods (in-depth interviews) and analysis to understand decision-making factors influencing PrEP adherence and alcohol use over time. Priority populations, including those engaging in alcohol use, need to increase engagement in the PrEP Care Continuum to optimize HIV prevention. Clinical research has yet to focus on interactions between PrEP, alcohol use and GI adverse events. This study may have important implications for mitigating a salient challenge to PrEP adherence and persistence (side-effects) and elucidating, from clinical and public health standpoints, factors promoting maintenance in the PrEP care continuum.