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

摘要 截至3月25日，2019年新型SARS-CoV-2冠状病毒病（COVID-19）已感染近1.25亿人 造成全球270多万人死亡。波多黎各的人口面临更高的新冠病毒风险- 19，由于人口中存在健康差距，老年人比例高于 整个美国。现在有超过105，000例COVID-19确诊病例，比2019年大幅增加。 2020年3月22日报告了64例感染病例。预计这些案件将继续 尽管当地政府提供了疫苗来减缓疾病的传播， 到目前为止，约有10%的人口已全部接种疫苗。这种可怕的情况与正在进行的阿片类药物 这种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。是 注射吸毒者感染包括HIV-1在内的传染病的风险很高， 现在可能又是新冠肺炎这些合并感染者的疾病进展可能非常不同 那些不注射的人。已知HIV-1感染与组织中的淋巴耗竭有关 并诱导全身炎症。由此导致的PWID对SARS-CoV-2的不适当免疫激活 感染可增强HIV-1复制，导致T细胞过早老化，促进HIV-1疾病 进展，并可能加强炎症的影响和COVID-19引起的疾病过程。的 一项拟议的研究将利用波多黎各一个成熟的注射毒品使用者队列， 注射毒品使用率达到历史最高水平，艾滋病毒发病率不成比例地与 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 对有和没有HIV-1的PWID进行研究，以确定SARS-CoV-2感染的流行率及其HIV-1病毒载量， 炎症，由于COVID-19和HIV-1感染导致的疾病进展。目前正在进行的纵向队列研究 在波多黎各进行的PWID研究将使我们的研究小组能够检验SARS-CoV-2感染HIV+的假设 PWID会加剧炎症，进而加剧HIV复制、疾病进展和HIV治疗 失败这一假设将通过三个具体目标进行检验：目标1，扩大我们目前的HIV-1队列研究 感染的PWID，与非PWID HIV未感染的对照组，以支持对 基线和随访时COVID-19的发病率和影响。目的2，定量SARS-CoV-2和HIV-1， 1血液样品中的病毒载量、细胞免疫表型和炎症介质，以及微生物 在基线和纵向随访这些病例的HIV疾病进展。目标3，关联 COVID-19对HIV-1病毒载量、细胞免疫表型、炎症介质和 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的其他州， 可能会导致制定预防HIV+ PWID中HIV和COVID-19疾病进展的策略。

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.