Biomarkers for Dysbiosis-Related HIV-Associated Cognitive Disorders among Persons Who Inject Drugs in Puerto Rico

摘要 截至3月25日，新型SARS-CoV-2冠状病毒病2019(新冠肺炎)已感染近1.25亿人 在全球造成超过270万人死亡的个人。波多黎各的人口患COVID的风险很高- 19由于人口中存在的健康差距以及老年人所占比例高于 美国作为一个整体。目前有超过105,000例新冠肺炎确诊病例，比去年同期大幅增加 就在一年前的2020年3月22日，报告了感染病例。预计案件将继续增加。 尽管当地州长提供了疫苗来减缓疾病的传播，但只有 到目前为止，约有10%的人口完全接种了疫苗。这种可怕的情况与正在进行的阿片类药物有关 这一流行病与美国许多其他地区目前的阿片类药物注射发病率相似。它是 公认的是，注射毒品(PWID)的人患传染病的风险很高，包括艾滋病毒-1， 现在可能还有新冠肺炎。这些合并感染的人的疾病进展可能非常不同。 来自那些不注射的人。已知HIV-1感染与组织中的淋巴样细胞耗竭有关 并引发全身炎症。PWID对SARS-CoV-2的不适当免疫激活 感染可能会增强HIV-1的复制，导致T细胞过早老化，从而促进HIV-1疾病 进展，并可能加强炎症的影响和新冠肺炎的病程。这个 拟议的研究将利用波多黎各成熟的注射吸毒者队列，那里有 注射吸毒史上的高水平和艾滋病毒发病率与 吸毒。我们建议的补充研究的总体目标是扩大和利用我们目前的纵向 HIV-1感染和未感染的PWID研究，以确定SARS-CoV-2感染的流行率及其HIV-1病毒载量， 新冠肺炎和艾滋病毒-1感染引起的炎症、疾病进展。目前正在进行的纵向队列 波多黎各对PWID的研究将使我们的团队能够检验SARS-CoV-2感染HIV+的假设 PWID会加剧炎症，进而加剧艾滋病毒复制、疾病进展和艾滋病毒治疗 失败。这一假设将通过三个具体目标进行检验：目标1，扩大我们目前对HIV-1的队列研究 感染的PWID，与非PWID HIV未感染的对照组一起支持前瞻性评估 基线和随访时新冠肺炎的发生率和疗效。目的2，对SARS-CoV-2和HIV-2进行量化 1血样中的病毒载量、细胞免疫表型和炎症介质，以及微生物 基线和纵向上的生物失调伴随着这些病例的艾滋病毒疾病进展。目标3，关联 新冠肺炎对HIV-1病毒载量、细胞免疫表型、炎性介质和免疫球蛋白的影响 神经认知功能以及疾病进展，同时控制艾滋病毒和注射药物使用状态 以及与吸毒有关的社会行为因素。结果可以翻译到美国其他州和 可能导致制定预防艾滋病毒和新冠肺炎病在艾滋病毒+PWID中进展的战略。

ABSTRACT As of March 25, the novel SARS-CoV-2 coronavirus disease 2019 (COVID-19) has infected almost 125 million individuals causing over 2.7 million deaths worldwide. Puerto Rico's population is at a heightened risk of COVID- 19 due to the existing health disparity in the population and its higher proportion of elderly people compared to the US as a whole. There are now over 105,000 confirmed cases of COVID-19, a substantial increase from the 64 infected cases reported just over year ago on March 22, 2020. It is expected that the cases will continue to increase even though vaccines are provided by the local governor to slow the spread of the disease but only about 10% of the population were fully vaccinated so far. This dire situation is coupled to the ongoing opioid epidemic that parallels the current opioid injection incidence in the many other parts of the United States. It is well established that people who inject drugs (PWID) are at high risk for infectious diseases, including HIV-1, and now possibly COVID-19. These co-infected individuals are likely to have disease progression very different from those who do not inject. It is known that HIV-1 infection is associated with lymphoid depletion in tissues and induces systemic inflammation. The resulting inappropriate immune activation in PWID upon SARS-CoV-2 infection may enhance HIV-1 replication, lead to premature aging of T cells to promote HIV-1 disease progression, and likely potentiate the effects of inflammation and disease course due to COVID-19. The proposed study will make use of a well-established cohort of injection drug users in Puerto Rico, where there is a historically high level of injection drug use and an HIV incidence rate that is disproportionately associated with drug use. The overall objective of our proposed supplement study is to expand and leverage our current longitudinal study on PWID with and without HIV-1, to determine the prevalence of SARS-CoV-2 infection and its HIV-1 viral load, inflammation, disease progression due to both COVID-19 and HIV-1 infections. The current ongoing longitudinal cohort study of PWID in Puerto Rico will allow our team to test the hypothesis that SARS-CoV-2 infection of HIV+ PWID intensifies inflammation that, in turn, exacerbates HIV replication, disease progression and HIV treatment failures. This hypothesis will be tested via three specific aims: Aim 1, Expand our current cohort study of HIV-1 infected PWID, with a non-PWID HIV uninfected control group to support a prospective evaluation of the incidence and the effects of COVID-19 at baseline and at follow-ups. Aim 2, Quantify the SARS-CoV-2 and HIV- 1 viral loads, cellular immune-phenotypes and inflammatory mediators in blood samples, and microbial dysbiosis at baseline and longitudinally followed these cases for HIV disease progression. Aim 3, Correlate the effects of COVID-19 on the HIV-1 viral loads, cellular immunophenotypes, inflammatory mediators and neurocognitive functions, as well as disease progression, while controlling for HIV and injection drug use status and socio-behavioral factors associated with drug use. The results is translatable to other states in the U.S. and may lead to the development of strategies to prevent HIV and COVID-19 disease progression in HIV+ PWID.