VALacyclovir for Inflammation AttenuatioN Trial Pilot (VALIANT Pilot)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Percentage activated CD8+ T-cells
研究概览
简要总结
The purpose of this study is to compare the levels of immune and inflammatory markers among HIV-1, HSV-2 co-infected adults achieving plasma HIV RNA suppression to <50 copies/mL, between those randomized to valacyclovir and placebo, over a twelve-week intervention period.
详细描述
Highly active antiretroviral therapy (HAART) has dramatically reduced HIV-1 infection (herein referred to as 'HIV') related morbidity and mortality, transforming an invariably fatal disease into a manageable, chronic condition. Yet even HAART-treated HIV infection is characterized by chronic systemic inflammation and immune activation. This systemic inflammatory response is composed of multiple components, and can be quantified by measuring markers of immune activation, inflammatory cytokines, acute phase reactants, endothelial activation markers, and markers of microbial translocation. This inflammation is clinically relevant, as it may contribute directly to HIV disease progression and non-AIDS related morbidity and mortality in HIV-infected patients. Because this inflammation persists even in the context of suppressive HAART, albeit at modestly decreased levels, adjunctive therapeutic strategies to attenuate this persistent inflammatory response are therefore needed. Herpes simplex virus type 2 is a common, clinically important co-infection seen in individuals living with HIV infection, and may contribute to this ongoing inflammation. This pilot trial will investigate whether short-term valacyclovir for HSV-2 suppression can decrease systemic inflammation in HAART-treated, HIV-1, HSV-2 co-infected individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adult (aged 18 years or older)
- •documented HIV-1 infection (determined by EIA and Western blot)
- •documented HSV-2 seropositivity (determined by ELISA during screening)
- •no use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study
- •sustained plasma HIV RNA<50 copies/mL on HAART for at least 12 months
- •no active opportunistic infection for at least 12 months
排除标准
- •hepatitis C co-infection
- •hepatitis B co-infection
- •pregnancy or actively planning to become pregnant
- •receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.)
- •Estimated creatinine clearance <30 mL/min
- •Other medical condition likely to cause death within 24 months
- •Enrolled in any other interventional clinical trial
研究组 & 干预措施
High dose valacyclovir
Valacyclovir 1g po BID
干预措施: Valacyclovir (Drug)
Low dose valacyclovir
Valacyclovir 500mg po BID
干预措施: Valacyclovir (Drug)
Placebo
Inert placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage activated CD8+ T-cells
时间窗: 12 weeks
Percentage of CD8+ T-cells co-expressing CD38 and HLA-DR
次要结局
- CD4 cell count(12 weeks)
- Inflammatory markers(12 weeks)
- Acyclovir-resistant HSV(18 weeks)
- Drug-related adverse events(18 weeks)
- HSV reactivations(12 weeks)
- Virologic blips(12 weeks)