Impact of Cannabis on Inflammation and Viral Persistence in Treated HIV/SIV

描述：全世界有3500万艾滋病毒感染者，改善这些人的健康面临巨大挑战。抗逆转录病毒疗法抑制艾滋病毒复制，从而预防艾滋病并降低总死亡率；然而，抗逆转录病毒疗法并不能完全恢复健康。事实上，尽管病毒血症得到持续抑制，但由于残留的艾滋病毒持续存在，个体不能停止抗逆转录病毒疗法，而且如果停止抗逆转录病毒疗法，病毒反弹是不可避免的。残留的HIV病毒库与持续的炎症有关。大麻在美国是一种广泛使用的药物，大麻素等大麻衍生物通常用于治疗癌症等严重疾病的恶心和恶病质。几项研究表明，大麻素具有改变免疫反应和减少体内炎症的倾向。我们假设，在art治疗的HIV感染背景下使用大麻可能会减少炎症和持续的HIV库。在这里，我们大胆地建议通过测量每天报告使用大麻的HIV感染者的血液和胃肠道（GI）组织中的炎症、免疫和HIV库来验证这一假设。此外，我们将评估机制大麻素抗炎活性体外使用大麻素受体激动剂共培养。此外，我们将利用非人类灵长类动物SIV感染模型来测试这一非常规想法的因果关系，通过使用大麻素治疗ART治疗的SIV感染猕猴，以评估对SIV库和炎症的影响。我们拥有一支优秀的研究团队，我们将评估以下内容：全球系统生物学，包括物种特异性转录分析和生物信息学；(2)。HIV和SIV病毒库使用新的检测方法来测量整合病毒、总病毒和诱导病毒；(3)。炎症与免疫细胞亚群的免疫表型；（iv）系统微生物易位和胃肠道屏障完整性；(v)血液和胃肠道中的药物水平和动力学。我们相信，这些拟议的研究将有助于更好地了解与艾滋病毒库相关的各个方面，并可能提供一种新的治疗方法，利用滥用药物，开发一种治愈艾滋病毒的方法。

DESCRIPTION: With 35 million HIV-infected individuals worldwide, the challenge to improve health in these individuals is vast. Antiretroviral therapy (ART) suppresses HIV replication, which prevents AIDS and reduces overall mortality; however ART does not fully restore health. Indeed, despite sustained suppression of viremia, individuals cannot discontinue ART as residual HIV persists, and virus rebound is inevitable if ART is discontinued. This residual HIV reservoir is associated with ongoing inflammation. Cannabis is a widely used drug in the United States, and derivatives of cannabis such as cannabinoids are commonly used in treatment of nausea and cachexia in severe conditions such as cancer. Several studies have demonstrated that cannabinoids have the propensity to alter immune responses and decrease inflammation in vivo. We hypothesize that cannabis use in the context of ART-treated HIV infection may decrease inflammation and the persistent HIV reservoir. Here, we provocatively propose to test this hypothesis in humans by measuring inflammation, immunity, and the HIV reservoir from blood and gastrointestinal (GI) tissues from HIV-infected individuals who report using cannabis daily compared to those reporting no drug use. Furthermore, we will assess mechanisms of cannabinoid anti- inflammatory activity ex-vivo using cannabinoid receptor agonists in co-cultures. In addition, we will exploit the non-human primate model of SIV infection to test causality of this unconventional idea, by treating ART- treated, SIV infected macaques with cannabinoids to assess the effects on SIV reservoir and inflammation. With an outstanding team of researchers, we will assess the following: (i.) Global systems biology, including species-specific transcriptional analysis and bioinformatics; (ii.) The HIV and SIV reservoir using novel assays to measure integrated, total and inducible virus; (iii.) Inflammation and immunophenotype of immune cell subsets; (iv.) Systemic microbial translocation and GI tract barrier integrity; and (v.) drug levels and kinetics in blood and GI tract. We believe these proposed studies will be integral to better understanding facets associated with the HIV reservoir and may provide a novel therapeutic approach, exploiting a drug of abuse, towards development of an HIV cure.