The COVID-19 vaccine efficacy among people living with and without HIV: a real-world data approach

项目总结/摘要 有效和持久的COVID-19疫苗有可能极大地改变COVID-19大流行。 2019冠状病毒病疫苗研发取得显著成就 观察到 在大型的随机控制的 试验中，发现几种疫苗在预防症状性COVID-19方面是安全有效的。 尽管疫苗效力水平很高，但一小部分完全接种疫苗的人（即，收到所有 FDA授权的COVID-19疫苗的推荐剂量）将出现症状或无症状 SARS-CoV-2感染，称为COVID-19疫苗突破性感染（以下简称 “突破性感染”）。免疫功能低下的人，如艾滋病毒感染者（PLWH）， 新冠病毒相关疾病、住院和死亡的风险增加。因此，确保有效性 艾滋病病毒感染者和艾滋病患者的COVID-19疫苗接种工作迫在眉睫。然而，COVID-19疫苗在艾滋病毒携带者中的有效性仍然存在， 不清楚，因为PLWH没有代表性地包括在疫苗功效试验中，并且没有考虑到 在现有的研究免疫功能低下人群中疫苗有效性的努力中， 现实世界中的人口。了解COVID-19疫苗在现实环境中的有效性对于 帮助疾病监测并为今后的加强疫苗分发提供信息。在NIH支持下（R 01 AI 127203） 自2017年以来，我们一直在利用大数据方法研究12，203名PLWH的治疗差距 2005-2020年期间在南卡罗来纳州（SC）被诊断为艾滋病毒感染者（“艾滋病毒队列”）。也支持 NIH（R 01 AI 127203 - 04 S1），我们的团队自2020年6月起建立了南卡罗来纳州COVID-19队列（S3 C） 通过整合患者的电子健康记录（EHR）与新冠肺炎前一年的医疗保健利用数据。 在这项探索性研究中，我们将检索来自南卡罗来纳州的患者级免疫记录 全州免疫在线网络（SIMON），并将该数据库与“艾滋病毒队列”数据库合并， 通过倾向评分匹配鉴定接种疫苗PLWH和非PLWH对照组。S3C 队列数据，其中包括医疗保健遭遇和COVID-19诊断信息，将与 HIV队列和SIMON数据集定义突破性感染。随着多种数据的整合 来源和先进的数据分析，目前的探索性研究首先旨在表征和比较 突破性感染（例如，患病率和疾病严重程度），然后 检查艾滋病毒标志物和艾滋病毒治疗是否在感染者和病毒携带者中对COVID-19疫苗的有效性发挥作用 人群，同时调整关键混杂因素（例如，既往COVID-19诊断，合并症，当地 COVID-19发病率）。拟议的研究是创新和重要的，因为了解新冠病毒- 19艾滋病毒感染者和非艾滋病毒感染者之间的疫苗效力对于支持知情的疫苗接种决策至关重要 在临床实践中。将PLWH表征为具有较高的突破性感染风险（低CD 4计数， 未抑制的病毒载量）可能有助于制定指导，以增强对COVID-19风险的保护。

Project Summary/Abstract Effective and durable COVID-19 vaccines hold the potential to dramatically alter the COVID-19 pandemic. Remarkable achievement of COVID-19 vaccine development was observed in large, randomized-controlled trials, where several vaccines were found to be safe and efficacious in preventing symptomatic COVID-19. Despite the high level of vaccine efficacy, a small percentage of fully vaccinated persons (i.e., received all recommended doses of an FDA-authorized COVID-19 vaccine) will develop symptomatic or asymptomatic infections of SARS-CoV-2, which is referred to as COVID-19 vaccine breakthrough infections (hereafter as “breakthrough infections”). Immunocompromised individuals, such as people living with HIV (PLWH), appear to be at an elevated risk of COVID-related illness, hospitalization, and death. Thus, ensuring the effectiveness of COVID-19 vaccine in PLWH is pressing. However, the efficacy of COVID-19 vaccine among PLWH remains unclear because PLWH were not representatively included in the vaccine efficacy trials and did not account for a large proportion in the existing efforts to investigate vaccine efficacy among immunocompromised population in the real-world. Understanding COVID-19 vaccine efficacy in real-world settings is critical to helping disease monitoring and inform future booster vaccine distribution. With NIH support (R01AI127203) since 2017, we have been utilizing a Big Data approach to examine the treatment gaps among 12,203 PLWH who were diagnosed with HIV during 2005-2020 (‘HIV Cohort’) in South Carolina (SC). Also supported by NIH (R01AI127203-04S1), our team have established a South Carolina COVID-19 cohort (S3C) since 06/2020 by integrating patients’ electronic health records (EHR) with one-year pre-COVID healthcare utilization data. In this exploratory study, we will retrieve the patient-level immunization records from the South Carolina Statewide Immunization Online Network (SIMON) and merge this database with ‘HIV Cohort’ database to identify vaccinated PLWH and a comparison group of non-PLWH via propensity score matching. The S3C cohort data, which includes healthcare encounters and COVID-19 diagnosis information, will be merged with HIV Cohort and SIMON datasets to define the breakthrough infections. With the integration of multiple data sources and advanced data analytics, the current exploratory study first aims to characterize and compare the breakthrough infections (e.g., prevalence and disease severity) between PLWH and non-PLWH and then examine whether HIV markers and HIV treatment play a role in COVID-19 vaccine efficacy within the PLWH population while adjusting for key confounders (e.g., prior COVID-19 diagnosis, comorbid conditions, local COVID-19 incidence). The proposed research is innovative and significant because understanding the COVID- 19 vaccine efficacy among PLWH and non-PLWH is essential to support informed vaccination decision-making in clinical practice. Characterizing PLWH at higher risk of breakthrough infections (low CD4 counts, unsuppressed viral load) may help to develop guidance to augment their protection against risk of COVID-19.