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 传播风险的药物治疗方案 个人，有助于帮助实现国家艾滋病毒预防目标。然而，临床上的副作用， 尤其是那些影响胃肠道 (GI)（恶心、呕吐、食欲不振）、肝肾损伤的疾病 结果可能会抑制 PrEP 的持续性。重要的是，PrEP 使用者经常饮酒可能会相互作用 与 PrEP 一起使用，会加剧 PrEP 相关的胃肠道不良反应，从而影响 PrEP 的持续性。 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 （菌群失调）。尽管 PrEP、酒精及其联合使用可能对患者产生重要影响 肠道菌群失调和随后的 PrEP 持续性，很少有研究来阐明这种相互作用，而且很少有研究能够阐明这种相互作用。 尝试解决这个问题。此外，很少有研究探索有关酒精的决策过程 PrEP 用户的 PrEP 使用率和依从性。为了解决这些研究空白，本研究将 采用以下目标。目标 1：定性探索酒精使用影响的机制 通过 PrEP 连续体进行运动，并了解早期干预和治疗如何 方法影响酒精使用和 PrEP 依从性。目标 2：研究 SBIRT 的有效性 预防有害酒精使用的干预措施及其对 PrEP 使用者肠道菌群失调的影响。内 在这项纵向队列研究中，我们将确定受酒精影响的参与者及其使用模式 从间歇性到长期（从事有风险或有害的使用）。目标 3：确定 肠道微生物组的改变（菌群失调）、肠道稳态、全身炎症和 PrEP 使用者中与危险饮酒相关的肝病标志物。从本地招聘 PrEP 诊所，我们将确定肠道微生物组、肠道稳态、全身炎症的变化 以及与酒精和 PrEP 使用相关的肝病标志物。我们还将执行随机对照 在 PrEP 用户中进行的试验表明，饮酒量增加，以测试筛查的有效性，简介 干预和转诊治疗 (SBIRT) 干预措施，以减少饮酒并检查后续情况 与照常接受治疗的个体和未接受 PrEP 的个体相比，对肠道微生物组的影响 证明饮酒量增加。最后，我们将采用定性方法（深度访谈）和 分析以了解随着时间的推移影响 PrEP 依从性和饮酒的决策因素。优先级 人群，包括那些酗酒的人群，需要更多地参与 PrEP 护理 继续优化艾滋病毒预防。临床研究尚未关注 PrEP、 饮酒和胃肠道不良事件。这项研究可能对缓解显着问题具有重要意义 临床和公众对 PrEP 依从性和持久性（副作用）的挑战和阐明 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.