Individualized Antiretroviral Therapy: Impact of Pharmacogenetic and Therapeutic Drug Monitoring in the Safety and Efficacy of First Line Antiretroviral Therapy in Patients With HIV Infection
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 190
- 试验地点
- 2
- 主要终点
- Feasibility of implementation of a multicenter study to analyze pharmacological adequation and therapeutic drug monitoring of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection
研究概览
简要总结
The efficacy and safety of antiretroviral therapy and the damage caused by chronic inflammation in the presence of the virus has recently lead to the consideration of initiating antiretroviral therapy earlier than what is required to prevent opportunistic diseases.
Although there may be subtle differences, all recommended antiretroviral combinations for first-line therapy are considered equally effective. Nevertheless, treatment success requires high levels of adherence, which is linked to tolerability and the minimization of adverse effects.
The genes coding the enzymes that are involved in the antiretroviral clearance pathways and the transmembrane transport of drugs are known. These genetic variations can determine the interindividual variations in plasma concentration with the same doses. Both pharmacogenomics (PG) and therapeutic drug monitoring (TDM) may contribute to the individualization of therapy in different chronic conditions through dosing optimization and are associated with a lower risk of concentration-dependent toxicity and potentially greater efficacy. The use of these strategies in the context of antiretroviral therapy is in early stage of development.
Following, our main hypothesis is that PG + TDM dose adjustment of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection is non-inferior in terms of efficacy, has improved safety, and shows a better cost/effectiveness profile than the standard approach with non adjusted doses.
To evaluate our hypothesis we developed this multicenter randomized clinical trial, where patients from 4 clinical sites in Buenos Aires will be included in the protocol and randomized to standard of care (SOC) or pharmacological adaptation (PA) -PA: PG + TDM. For the pharmacogenomics determination, we developed a multiplex approach including main polymorphisms of CYP2B6, CYP2A6, CYP3A4 y ABCB1 for efavirenz; and UGT1A1, ABCB1 and CYP3A4 for atazanavir. Drug plasma levels will be analyzed with ultra-performance liquid chromatography (UPLC).
The main outcomes are to establish the usefulness of PG and TDM in determining the efficacy, safety and cost/effectiveness of a first-line antiretroviral therapy containing either efavirenz or atazanavir in patients with HIV infection who have not received prior antiretroviral therapy.
详细描述
I) General Objectives To establish the overall impact of pharmacogenomic (PG) analysis and therapeutic drug monitoring (TDM) for the selection of the proper dose of efavirenz or atazanavir in patients with an HIV infection who have not received prior antiretroviral treatment.
II) Specific objectives and working hypothesis Establish the usefulness of PG and TDM in determining the efficacy, safety and cost/effectiveness of a first-line antiretroviral therapy containing either efavirenz or atazanavir in patients with HIV infection who have not received prior antiretroviral therapy.
II b. Working Hypothesis Pharmacogenomic analysis and therapeutic drug monitoring dose adjustment of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection is non-inferior in terms of efficacy, has improved safety, and shows a better cost/effectiveness profile than the standard approach without dose adjustment.
III) Background III a. Introduction Combination antiretroviral therapy has modified the natural history of HIV infection in an unprecedented manner in medical history.
Today, the life expectancy of people with a chronic retroviral infection and access to treatment resembles that of the general population. The efficacy and safety of antiretroviral therapy and the damage caused by chronic inflammation in the presence of the virus has recently lead to the consideration of initiating antiretroviral therapy earlier.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Health Services Research
- 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
- •Adult patients with diagnosis of chronic HIV infection confirmed by Western blot and / or HIV viral load
- •Patients in whom (according to the judgment of the treating physician) antiretroviral therapy should be initiated and this treatment will be a regimen based on Efavirenz or Atazanavir.
- •Availability of a baseline genotyping test confirming the absence of primary resistance for the selected drugs.
- •Signature of the informed Consent Form
排除标准
- •Patients who remain untreated or those treated with a regimen that does not include efavirenz or atazanavir
- •Lack of understanding of the study characteristics or rejection to have samples taken for the pharmacological studies.
- •Patients who are not expected to continue their follow-up at the research center for at least one year
- •Patients with coinfections or comorbidities that prevent a dose adjustment of efavirenz or atazanavir based on pharmacological parameters.
结局指标
主要结局
Feasibility of implementation of a multicenter study to analyze pharmacological adequation and therapeutic drug monitoring of efavirenz or atazanavir in the initial antiretroviral treatment of naive patients with HIV infection
时间窗: 48 Weeks
Number of days between obtention of study samples and availability of test results (turnaround time)
次要结局
- Efficacy of antiretroviral treatment(48 weeks)
- Cost/effectiveness compared in both arms(48 Weeks)
- Frequency of adverse events(48 Weeks)
研究者
Waldo Horacio Belloso
MD
Hospital Italiano de Buenos Aires