Vaccines in a Time of Dual Pandemic: COVID-19 Vaccine in People With HIV
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Primary
研究概览
简要总结
This is a prospective, non-randomized observational study to examine SARS-CoV-2 vaccine immunogenicity, immune activation and HIV reservoirs in people with HIV infection in comparison with HIV-negative individuals, in those aged 55 or more.
As Canada is currently rolling out COVID-19 vaccines, the two most imminent vaccines are mRNA vaccines. These are the Pfizer-BioNTech COVID-19 vaccine given 3 weeks apart and the Moderna COVID-19 vaccine given 4 weeks apart. Given the unique storage requirements of these vaccines, it is expected that the Moderna vaccine will be used primarily in primary care clinics such as Maple Leaf Medical Clinic, Toronto. However, the protocol will also allow observational study of individuals being administered with the Pfizer-BioNTech vaccine if it is also available. The investigators predict general availability of both vaccines to the primary care population by March 1, 2021. Vaccination will occur as per clinical and public health guidelines. COVID-19 vaccines will not be administered as a part of this research study. This is a single site longitudinal study where 75 participants in total are followed over 48 weeks with blood draws and saliva sampling. The breakdown of study arms is described here:
• PWH Immune responders (n= 35): undetectable viral load for 1+ year, CD4 >500/uL, CD4/CD8 ratio >1 including individuals with a historical, low CD4 nadir
• PWH Immune non-responders (n= 10): undetectable viral load, CD4 <350/uL or CD4/CD8 ratio <0.75 for 1+ year
• PWH Low-level viremics (n= 10): low-level viremia (<1,000 copies/mL) for 1+ year, any CD4, any CD4/CD8 ratio
• HIV-negative control (n= 20): age and sex matched
详细描述
People with HIV (PWH) may experience an increased risk of COVID-19 related diseases or mortality upon SARS-CoV-2 infection1-5, and COVID-19 vaccines will play a significant role in combating the pandemic. Currently, there are two mRNA vaccines to be utilized in Ontario (Pfizer-BioNTech, Moderna), both with a two-dose regimen6,7. While data so far do not suggest any particular safety concerns for PWH, only a limited number of PWH have participated in COVID-19 vaccine trials, and they were recruited late during two recent large confirmatory approval studies. In addition, emergency approval review of the confirmatory trials for one of the vaccines did not include PWH in safety and efficacy calculations7,8, including PWH receiving antiretroviral therapy (ART) who present ongoing low-level viremia, immunosenescence and/or persistent immune activation. Nevertheless, PWH are encouraged to get vaccinated promptly while data collection continues.
A significant gap in our knowledge - and based on experience with vaccines administered to PWH for other pathogens9 - is whether COVID-19 vaccines may have any impact on ongoing chronic inflammation and other immune dysregulation that can exacerbate co-morbidity incidence or affect the dynamics of the human immunodeficiency virus (HIV) reservoir. Therefore, understanding how COVID-19 vaccines affect immune activation and HIV reservoirs in PWH is of paramount importance and may have implications for 38 million PWH globally. Furthermore, premature immunosenescence previously reported in PWH coupled with the heterogeneity of immune reconstitution following initiation of ART suggests that it will be crucial to determine whether COVID-19 vaccines can induce protective and robust immune responses both in the short-term and long-term, particularly in specific subgroups with diminished immunocompetence. Elucidating the effect of COVID-19 vaccines on immune activation and HIV reservoir as well as vaccine efficacy in PWH are critical but are unlikely to be evaluated by vaccine sponsors.
The investigators expect that our study population will not be included in the early priority administration of the COVID-19 vaccines in Ontario. Our target population is PWH over 55 of age often with comorbidities, who are likely to be offered vaccination within a most opportune window and convenient timeframe for this directed research.
Risk of COVID-19 in people with HIV (PWH)
Although data on the risk of COVID-19 on people with HIV (PWH) are limited, emerging evidence suggests that PWH may experience an increased risk of COVID-19 related diseases or mortality upon SARS-CoV-2 infection. For instance, a prospective observational study from the United Kingdom showed that after adjusting for several variables including sex, ethnicity, age and selected comorbidities, HIV-positive status remained significantly associated with an increased risk of day-28 mortality among individuals hospitalized for COVID-195. Another study from the United Kingdom also showed that PWH experience enhanced risk of COVID-19 mortality after adjusting for age, sex, deprivation, ethnicity, smoking and obesity (adjusted hazard ratio 2.59; 95% CI 1.74-3.84)3. Likewise, a population cohort study from South Africa also demonstrated that HIV is associated with COVID-19 mortality with an adjusted hazard ratio of 2.14 (95% CI 1.70-2.70)10. It is important to note, however, that several potential confounders were not included in these studies such as occupation and surrogate markers of HIV control11.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants will fall into any of the HIV-positive arms or the HIV-negative control arm. Inclusion criteria for HIV-positive participants are:
- •Ability to provide signed written informed consent
- •Documented HIV diagnosis for 1+ year
- •Antiretroviral therapy for 1+ year
- •55 years of age or older
- •Good general health as shown by medical history and screening laboratory tests at the screening visit:
- •Hemoglobin ≥ 85 g/L White blood cell (WBC) count = 3300 to 12,000 cells/mm3
- •Total lymphocyte count ≥ 800 cells/mm3
- •Platelets = 50,000 to 550,000/mm3
- •Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase < 5 times the institutional upper limit of normal (ULN); creatinine (Cr) ≤ institutional upper limit of normal; creatine phosphokinase (CPK) ≤ 2 times the institutional upper limit of normal not related to physical exertion
- •Inclusion criteria for HIV-negative participants are:
- •Ability to provide signed written informed consent
- •Negative HIV test at the screening visit
- •55 years of age or older
- •Stable clinical status and absence of acute illnesses as shown by medical history and screening laboratory tests at the screening visit:
- •Hemoglobin ≥ 85 g/L White blood cell (WBC) count = 3300 to 12,000 cells/mm3
- •Total lymphocyte count ≥ 800 cells/mm3
- •Platelets = 50,000 to 550,000/mm3
- •Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase < 5 times the institutional upper limit of normal (ULN); creatinine (Cr) ≤ institutional upper limit of normal; creatine phosphokinase (CPK) ≤ 2 times the institutional upper limit of normal not related to physical exertion
排除标准
- •There will be no exclusion criteria based on gender/gender identity, ethnoracial composition, language, socioeconomic status, mode of HIV acquisition or sexual orientation/identity. Any participant who requires language interpretation can and will be accommodated for by the participation of translators, either at the patient's choice and/or with the assistance of the translator services provided by local ASO organizations. Exclusion criteria include the following:
- •Participants who would have difficulty participating in a trial due to non-compliance
- •Participants with a history of anaphylaxis reaction to the COVID-19 vaccine components
- •Participants with any of the following abnormal laboratory results at the screening visit:
- •Hemoglobin < 85 g/L
- •Lymphocyte count < .750 X109/L
- •Platelet count < 50 X109/L or > 550 X109/L
- •AST or ALT > 5X the upper limit of normal
- •Creatinine > 250 µmol/L
- •Participant with a malignancy or undergoing chemotherapy
- •Participant with other significant underlying disease (non-HIV-1) that might impinge upon disease progression or death
- •Active infection with hepatitis virus (HAV, HBV, HCV) or tuberculosis
- •Prior surgery or radiation therapy within 30 days of study screening or receipt of any other experimental compound within 30 days of signing informed consent
- •Any concurrent condition requiring the continued use of immunoglobulin, antineoplastic agents, glucocorticoids (other than corticosteroid nasal spray for allergic rhinitis; topical or ophthalmic corticosteroids for acute, uncomplicated dermatitis or conjunctivitis; over the counter medications for acute, uncomplicated dermatitis for treatment period not longer than 14 days) or other immunomodulator medications (other than NSAIDS which will be allowed for any length of time)
- •Receipt of any blood product within 3 months prior to screening
- •Receipt of any vaccine within 1 month prior to screening
- •Active drug or alcohol use/dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
- •Any illness or conditions including acute illnesses that, in the opinion of the investigator, may affect the safety of the participant or the evaluation of any study endpoints
- •Any other conditions judged by the investigator that would limit the evaluation of a participant
- •Positivity for sexually transmitted infections at the screening visit
- •Use of any unproven registered and unregistered treatments for COVID-19; Administration of immunoglobulins and/ or any blood products within the three months preceding the planned administration of the vaccine candidate
- •Any confirmed or suspected immunosuppressive or immunodeficient state (except HIV infection for Group-3), asplenia, recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed)
- •For HIV-negative participants: immune-compromising conditions or on medication which suppresses the immune response.
结局指标
主要结局
Primary
时间窗: Week 24
Serum SARS-CoV-2 Neutralization assay (plaque reduction microneutralization assay) will be compared between HIV-positive and negative groups.
次要结局
- B-cell/memory(Weeks 0, 1, 2, 5, 6, 8, 24 and 48)
- Neutralization titers(Baseline and Week 48)
- IgG; RBD; NCP(Weeks 0, 1, 2, 5, 6, 8, 24 and 48)
- T cell(Week 24 and Week 48)
- COVID-19 Infection(Up to week 48)
- Salivary IgA(Week 5 and Week 24)
- Provirus(baseline, Week 24 and Week 48)
- Activation Parameters(Weeks 0, 1, 2, 5, 6, 8, 24 and 48)
- Cytokine and Chemokine(Weeks 0, 1, 2, 5, 6, 8, 24 and 48)
- B-cell/plasmablast(Weeks 0, 1, 2, 5, 6, 8, 24 and 48)
研究者
Mario Ostrowski
Clinical Professor
University of Toronto