Mechanisms of Immune Reconstitution & Reduced Immune Activation Following Darunavir-based ART
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Number of CD4+ T-cells in the Lamina Propria/mm2 Before and After 12 Months of Therapy Compared to Age-matched Control Volunteers Without HIV
研究概览
简要总结
Potent HIV suppression with Darunavir-based antiretroviral therapy (ART) will lead to repopulation of gastrointestinal-associated lymphoid tissue (GALT) cluster of differentiation (CD)4+ T-cell populations, normalization of systemic immune activation, and improved HIV-associated cardiovascular disease (CVD) risk.
详细描述
Rationale Infection with HIV causes significant morbidity and mortality, even among individuals who are virologically suppressed with combination anti-retroviral therapy (ART). ART is effective in prolonging life and enabling individuals who are HIV positive to live near-normal life spans. However, these individuals are increasingly developing a number of chronic diseases of aging, such as atherosclerotic cardiovascular disease (ASCVD). The proposed studies will examine the role of highly active antiretroviral therapy in restoring the mucosal immunity and the systemic effect on immune activation, bacterial translocation, and change in HIV-associated cardiovascular disease risk.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing to sign consent form
- •Naïve to ART (remote ART use >5 years will be considered on a case by case basis)
- •No known GI or cardiovascular disease
- •Between the ages of 18 and 60
- •No active opportunistic infections or therapy for acute OI within 30 days of entry. Subjects can be on secondary prophylaxis with a history of AIDS defining illness.
- •All women of childbearing potential (WCBP) must have a negative urine pregnancy test before any of the invasive or radiation exposure study procedures.
- •Normal population should be free of chronic metabolic conditions such as diabetes, hypercholesterolemia, or coronary artery disease
- •There are no CD4+ T-cell count or HIV plasma viral load restrictions.
排除标准
- •Abnormal coagulation parameters (PT>1.2 upper limit of normal (ULN))
- •Thrombocytopenia (platelet count <50.000 within 6 weeks)
- •Contra-indications to upper endoscopy or conscious sedation
- •Anemia (>grade 1 [appendix 1])
- •Aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation cascade are prohibited within 1 week of endoscopy.
- •Renal insufficiency (serum Creatinine >1.2 ULN)
- •History of chronic proteinuria that could impact viread use.
- •Allergy to contrast used for CT angiography
- •Requirement to take medications that are contraindicated with study ART regimen.
研究组 & 干预措施
HIV positive naive to ART
HIV subjects will receive open-label darunavir 800 mg in combination with ritonavir 100 mg tablets and fixed-dose combination viread + emtricitabine (Truvada®) to be taken once daily without regard to food. Subjects will undergo upper endoscopy, CT cardiac angiogram, intimal-medial thickening, and peripheral blood collection before and after 12 months of ART.
干预措施: darunavir with ritonavir and fixed-dose viread+emtricitabine daily (Drug)
结局指标
主要结局
Number of CD4+ T-cells in the Lamina Propria/mm2 Before and After 12 Months of Therapy Compared to Age-matched Control Volunteers Without HIV
时间窗: Baseline, 12 months
CD4+ T-cells in the lamina propria/mm2 before and after 12 months of therapy compared to age-matched control volunteers without HIV.
次要结局
- Change in Percentage of Total Artery Diameter(Baseline, 12 months)