Immune Dysfunction in HIV + Opiod Users

HIV阿片使用者的免疫功能障碍

• 批准号: 10845088
• 负责人: Savita Pahwa
• 金额: $ 38.11万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10845088
• 关键词: ATAC-seq; Affect; Age; Age Distribution; Aging; Analgesics; Antibodies; Antibody Formation; Antibody Response; Antigens; B-Lymphocytes; Binding; Biological Assay; CD4 Positive T Lymphocytes; Cell Communication; Characteristics; Chronic; Cities; Data; Databases; Dependence; Elderly; Enrollment; Epidemic; Exhibits; Grant; HIV; HIV Infections; HIV/AIDS; Helper-Inducer T-Lymphocyte; Hemagglutination; Hemagglutinin; Immune System Diseases; Immune response; Immune system; Immunity; Immunoglobulin G; Immunoglobulin M; Impairment; Incidence; Inflammation; Inflammatory; Inflammatory Response; Influenza Hemagglutinin; Influenza vaccination; Interferons; Investigation; Morphine; Nature; Neuraminidase; Opioid; Outcome; Output; Participant; Pathway interactions; Pattern; Peripheral; Persons; Population; Recording of previous events; Role; ST14 gene; Signal Induction; Signal Pathway; Signal Transduction; T-Cell Activation; T-Lymphocyte; Testing; Universities; Vaccine Antigen; Vaccines; Western Blotting; addiction; age effect; age group; age related; aged; chronic pain; cohort; cytokine; expectation; flu; follow-up; immune activation; influenza virus vaccine; injection drug use; member; memory CD4 T lymphocyte; monocyte; non-opioid analgesic; opioid abuse; opioid epidemic; opioid use; opioid use disorder; parent grant; recruit; response; seasonal influenza; study population; tool; transcriptome sequencing; vaccine response

Abstract Miami is at the epicenter of the US HIV/AIDS epidemic, leading U.S. cities in HIV incidence with the highest HIV infection case rate (51.2 per 100,000). Concurrently, dependence on or addiction to opioids is widely prevalent, more so in the HIV+ population that is vulnerable for multiple reasons including need for pain medications. The University of Miami is actively pursuing projects to curb HIV and opioid epidemics. We are currently conducting a study to investigate the impact of opioids on immune responses in PWH and PWoH as compared to non- opioid users with and without HIV. The premise for the primary grant (R01DA051202) was that HIV infection and opioids are independently harmful for the immune system. HIV impairs immunity that is associated with persisting immune activation even after durable virologic control, while opioids (OP) are immunosuppressive. Together, they can potentially compound the damage to the immune system, leading us to hypothesize that people with HIV (PWH) who abuse opioids are likely to damage their immune system which would grossly blunt the immune response to influenza vaccine. We enrolled 4 study groups on the basis of HIV status and chronic opioid use: HIV+OP+, HIV+OP-, HIV-OP+, HIV-OP- using stringent enrollment criteria to evaluate flu vaccine induced Ab responses as well as B/T cell interaction by study of peripheral T follicular helper cells (Tfh), the memory CD4 T cells that are intimately involved in stimulating B cells to produce Ab to vaccine antigens. We found that the HIV+OP+ group exhibited high level of inflammation and immune activation (IA). We used rigorous statistical tools, and determined that Opioids were the major drivers of inflammation while HIV was the main driver of cellular immune activation of T cells. Unexpectedly, we found that people with OUD had better Ab responses based on titer and fold increase from baseline than non-opioid using population, and the same was true for HIV+OP+ group in comparison to HIV+OP- group, which had the lowest Ab responses as expected. Age in the study population as a whole was inversely correlated with Ab responses, but we do not have sufficient numbers of aged people with OUD in our cohort to assess if age was influencing the immune response or whether OP also circumvent the deleterious effects of HIV or Aging on Flu vaccine response. In this supplement, we plan to enroll additional “old” OUD participants to assess the impact of age on the immune response and understand whether OP use can circumvent the deleterious effects of Aging or of HIV on Flu vaccine responses. We will investigate if underlying mechanisms involve a unique inflammatory cytokine pattern or signaling pathways in monocytes that affect their cytokine output. We also plan to examine the nature of the Flu Ab secreted to assess whether the secreted Ab has functional diversity.

摘要