Immediate Initiation of Antiretroviral Therapy During Acute HIV Infection
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 74
- 试验地点
- 2
- 主要终点
- Safety and tolerability of immediate Dolutegravir plus Emtricitabine/Tenofovir administered to acutely infected HIV patients.
研究概览
简要总结
The purpose of this study is to identify and provide immediate antiretroviral therapy to a cohort of HIV-infected individuals with very early HIV infection (estimated date of infection within the last 90 days). The primary aim of the study is to evaluate whether initiation of dolutegravir plus emtricitabine/tenofovir during acute/early HIV infection leads to protection of CD4+ T cells and other immune cells in the peripheral blood and lymphoid tissue from infection.
详细描述
Although ART decreases HIV-associated mortality, it does not appear to completely restore immune health, for reasons that remain unclear. In addition, while HIV prevention approaches have led to significant successes in decreasing the incidence of new HIV infection over the past few years, the epidemic continues to grow both locally and globally. While complete eradication may not currently be feasible, a "functional cure" in which patients are able to indefinitely maintain undetectable viral loads in the absence of therapy may be an attainable immediate goal. Studying patients with early HIV infection and immediate ART will provide a unique opportunity to investigate the pathophysiology of the earliest stages of HIV infection and may help identify the virologic/immunologic predictors of a functional cure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide written informed consent
- •Male or female, age ≥18 years
- •Acute HIV infection with a negative or indeterminate HIV-1 antibody test and plasma HIV-1 RNA > 40 cp/ml, OR clinical history consistent with new HIV infection in the last 90 days.
- •Antiretroviral therapy untreated or recently initiated (within 7 days)
- •Participant must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
- •All participants must agree not to participate in a conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization)..
- •When participating in sexual activity that could lead to pregnancy, female participants must agree to use a double barrier method of contraception for at least two weeks after discontinuation of study drug.
排除标准
- •Known severe kidney disease (CrCl < 60 ml/min via Cockcroft-Gault method)
- •Known severe hepatic impairment (Child-Pugh Class C)
- •Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •Participants with anticipated need for Hepatitis C virus (HCV) therapy during study
- •Concurrent treatment with dofetilide, oxcarbazepine, phenytoin, phenobarbital, carbamazepine, St. John's wort, or metformin
- •Serious illness requiring systemic treatment and/or hospitalization in the preceding 90 days prior to study enrollment
- •Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drugs in the preceding 90 days prior to study enrollment (e.g. IL-2, interferon-alpha, methotrexate, cancer chemotherapy)
- •Concurrent treatment with investigational drugs, or exposure to any investigational drugs in the preceding 90 days prior to study enrollment
- •Active drug or alcohol use or dependence that, in the opinion of the Principal Investigator, would interfere with adherence to study requirements
- •Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation
- •Pregnant or breastfeeding women.
- •For participants who agree to colorectal biopsy
- •Known blood coagulation disorder
- •Platelets < 50,000/mm^3
- •PTT > 2x upper limit of normal
- •Use of aspirin, NSAIDs, Plavix, Coumadin, or other blood thinners that cannot be stopped for clinical reasons for 5 days before and after each colorectal biopsy
- •Inflammatory colitis (e.g., Crohn's disease and/or ulcerative colitis) and/or any contraindications to sigmoidoscopy or colorectal biopsy such as peritonitis, active diverticulitis, or recent bowel surgery
研究组 & 干预措施
Dolutegravir+Emtricitabine/Tenofovir
Dolutegravir 50 mg PO daily plus Emtricitabine 200 mg/Tenofovir alafenamide 25 mg
干预措施: Dolutegravir (Drug)
Dolutegravir+Emtricitabine/Tenofovir
Dolutegravir 50 mg PO daily plus Emtricitabine 200 mg/Tenofovir alafenamide 25 mg
干预措施: Emtricitabine/Tenofovir (Drug)
结局指标
主要结局
Safety and tolerability of immediate Dolutegravir plus Emtricitabine/Tenofovir administered to acutely infected HIV patients.
时间窗: 6 months
The number of grade 2 or higher severity adverse events (AEs) or drug-related laboratory abnormalities that exceed a frequency of 5% over a 6 month study period.
次要结局
- Change in HIV reservoir size (cell-associated total DNA) in peripheral blood(5 years)
- Change in HIV reservoir size (cell-associated integrated DNA) in peripheral blood(5 years)
- Change in HIV reservoir size (cell-associated unspliced RNA) in peripheral blood(5 years)