Alternative Dosing Strategy for Anti-HIV Drugs
Concentration-Controlled Antiretroviral Therapy in Persons Experiencing Persistent Viremia
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.
研究概览
详细说明
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.
研究类型
注册
阶段
- 第四阶段
联系人和位置
学习地点
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Colorado
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Denver、Colorado、美国、80262
- University of Colorado Health Sciences Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria for Cohort I:
- HIV infected
- Receiving therapy with 3 or more antiretroviral medications and and willing to continue this regimen
- Achieved a greater than 1 log10 reduction in plasma HIV-RNA from baseline within 8 weeks after the start of current therapy
- Current plasma HIV-RNA levels greater than 500 copies/mL and less than 10,000 copies/mL
Inclusion Criteria for Cohort Cohort II:
- HIV infected
- Receiving antiretroviral therapy and have been determined to have had virologic failure
- Will or have been changed to a new antiretroviral regimen (addition of greater than one new antiretroviral agent), but have not received this new regimen for more than 4 weeks as of study entry
- HIV RNA of 2500 copies/mL or greater at screening
Exclusion Criteria:
- 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
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
研究衡量的是什么?
主要结果指标
结果测量 |
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Ability of the concentration-controlled strategies to achieve and maintain target concentrations
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safety and tolerability of pharmacologic intensification
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ability of pharmacologic intensification to achieve and maintain a sustained suppression in plasma HIV RNA
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次要结果测量
结果测量 |
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Cross clade neutralizing antibody
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cellular immunity
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合作者和调查者
调查人员
- 首席研究员:Courtney V. Fletcher, PharmD、University of Colorado, Denver
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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