Concentration-Controlled Antiretroviral Therapy in Persons Experiencing Persistent Viremia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 2
- 主要终点
- Ability of the concentration-controlled strategies to achieve and maintain target concentrations
研究概览
简要总结
Anti-HIV drugs are usually given to patients at fixed, standardized doses. This study will investigate alternative ways of dosing anti-HIV drugs to improve viral control.
Study hypothesis: The optimal dosage regimen required to obtain the maximum benefit from antiretroviral therapy is achieved with strategies that control for pharmacokinetic and pharmacodynamic variability among patients.
详细描述
While optimism for the benefits of antiretroviral therapy remain justified, the response to therapy varies widely. This variability arises because of differences among patients in virologic, immunologic, behavioral, and pharmacologic factors, all of which impact therapeutic success.
Antiretroviral agents are presently administered to adults in standard fixed doses. However, the same dose does not produce the same systemic and intracellular concentrations in all patients. Recent research has shown that adjusting the doses of antiretroviral agents to achieve target concentrations in plasma is associated with an improved anti-HIV response compared with standard dose therapy. This study will extend the paradigm of concentration-controlled therapy to develop intensified pharmacologic regimens for patients experiencing persistent viremia while receiving antiretroviral therapy.
Two approaches will be investigated: 1) a regimen that targets concentrations of each antiretroviral drug between the 50th and 75th percentile of expected concentrations in adults; and 2) a novel regimen in which the target concentrations are based upon a desired ratio between phenotypic drug susceptibility (IC90) and the concentrations of pharmacologically active moieties, specifically intracellular nucleoside triphosphates and unbound protease and nonnucleoside inhibitors.
Participants will be randomized to either one of the investigational approaches (Cohort II) or to a control group receiving standard dose therapy (Cohort I). There are two study visits in the first month; after the first month, study visits are scheduled monthly for five additional months. Study visits include laboratory tests of virologic and immunologic parameters, pharmacokinetic sampling, and adherence counseling and monitoring.
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
- 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
- 未提供
排除标准
- •Concurrent investigational antiretroviral agent
- •Malignancy, including Kaposi's sarcoma, requiring systemic chemotherapy
- •Active opportunistic infection requiring therapy within 14 days prior to study entry
- •Drug-resistant mutations that necessitate a change in antiretroviral regimen
- •Active drug or alcohol use or dependence
- •Certain laboratory abnormalities
- •Pregnant or breastfeeding
- •Known nonadherence with medications and scheduled clinic visits
- •Any medical condition that, in the opinion of the investigators, would preclude successful completion of the study
结局指标
主要结局
Ability of the concentration-controlled strategies to achieve and maintain target concentrations
ability of pharmacologic intensification to achieve and maintain a sustained suppression in plasma HIV RNA
safety and tolerability of pharmacologic intensification
次要结局
- cellular immunity
- Cross clade neutralizing antibody