Benefits and Risks of Early Antiretroviral Therapy in HIV-infected Adults in Abidjan, Côte d'Ivoire: Randomized Controlled Trial (ANRS 12136 TEMPRANO)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 2,073
- 试验地点
- 9
- 主要终点
- prevalence of HIV resistance (ANRS12253 associated study)
研究概览
简要总结
The Temprano trial is based on the following assumptions:
- ART initiation at CD4 counts <800/mm3 could significantly reduce the probability of severe HIV-related morbidity or death in the medium term.
- Tuberculosis and tuberculosis-related deaths are likely to represent a considerable proportion of morbidity and mortality among HIV-infected patients with high CD4 counts in sub-Saharan Africa. Therefore, 6-month Isoniazide Prophylaxis for Tuberculosis (IPT) and early ART could enhance each others efficacy.
详细描述
- The main individual benefit of very early ART initiation is likely a reduction in early severe AIDS-defining and non-AIDS-defining morbidity. While the diseases that might justify earlier initiation in high-income countries are generally non-infectious (non-AIDS-defining malignancies, renal diseases and cardiovascular diseases), the leading cause of early severe AIDS-defining morbidity in sub-Saharan Africa is tuberculosis and the main causes of severe non-AIDS-defining morbidity are non-invasive bacterial diseases. As a result of poor access to diagnosis and care, some HIV-infected people die from early infectious diseases before reaching current WHO criteria for starting ART.
- Although the Côte d'Ivoire National Tuberculosis Program (PNLT) does not authorize the use of prophylaxis against tuberculosis, it has allowed the Temprano trial to provide a six-month course of isoniazid (INH) prophylaxis to half of the study subjects. This will allow us to (i) put early ART in perspective with a early 6-month INH prophylaxis use, in a setting where tuberculosis is the first cause of severe HIV-associated morbidity; and (ii) to describe and assess the feasibility of a six-month course of INH prophylaxis among patients with high CD4 counts.
- Some drug toxicities are immediate but reversible. If early ART is compared to no ART in the short term, these toxicities may demonstrate erroneously that early ART is unfavorable. The risks and benefits of early ART initiation should therefore be evaluated over the long term. In the Temprano trial, we will: (i) follow patients for at least 30 months and analyze the primary outcome at 30 months; (ii) follow some study subjects for 80 months and evaluate the evolution of the ART efficacy / toxicity ratio from month 30 to month 80 as a secondary endpoint, to inform future policies if early ART is found to be beneficial at 30 months.
Main objective: To assess the benefits and risks of starting ART immediately and/or to receive a 6-month IPT among HIV-infected adults with CD4 counts <800mm3 and no criteria for starting ART immediately according to the most recent WHO guidelines.
Location: Abidjan, Côte d'Ivoire.
Methods: randomized 2x2 factorial superiority trial
Main inclusion criteria: (i) HIV-1 or HIV-1+2 infection; (ii) age >18 years; (iii) nadir CD4 count <800/mm3 and no criteria for starting ART immediately according to the most recent WHO guidelines; and (iv) no active tuberculosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 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
- •HIV-1 or HIV-1 + HIV-2 infection
- •Age >18 years
- •No ongoing active tuberculosis
- •Home address in any district of the greater Abidjan area
- •Written informed consent before any clinic visit or laboratory test
- •Clinical and immunologic status:CD4 counts <800/mm3 and no criteria for starting ART according to the most recent WHO guidelines
排除标准
- •Pregnant or breastfeeding women
- •HIV-2 infection alone
- •Clinical signs suggesting a severe disease (including tuberculosis) that has not yet been diagnosed, such as fever, wasting, diarrhea or unexplained cough (partial list)
- •Previous ART initiation
- •Known severe renal, cardiac or hepatic disease
研究组 & 干预措施
I
Standard of care
干预措施: Antiretroviral medications (Drug)
II
Standard of care+Isoniazid Prophylaxis:
干预措施: Antiretroviral medications+Isoniazid prophylaxis (Drug)
III
Early Antiretroviral therapy
干预措施: Antiretroviral medications (Drug)
IV
Early Antiretroviral therapy + Isoniazid prophylaxis
干预措施: Antiretroviral medications+Isoniazid prophylaxis (Drug)
结局指标
主要结局
prevalence of HIV resistance (ANRS12253 associated study)
时间窗: 30 month after ARV initiation
Death (all-cause), or severe HIV-related disease (AIDS-defining diseases, non-AIDS-defining malignancies, and non-AIDS-defining invasive bacterial diseases)
时间窗: 30 months
* Severe HIV-related disease are defined as AIDS-defining diseases, non-AIDS- defining malignancies, and non-AIDS-defining invasive bacterial diseases * Invasive bacterial diseases are defined as: bacteremia, or bacterial infection of any solid organ or aseptic cavity (eg: pneumonia, pleurisy, meningitis,pyomyositis, pyelonephritis, prostatitis, orchitis, epididymitis, salpingitis, endometritis, endocarditis, cholecystitis, visceral abscesses).
次要结局
- Adherence to treatment(30 months)
- Resistance to antiretroviral medications(30 months)
- Individual socio-economic factors(30 months)
- Changes in CD4 counts(30 months)
- Quality of life(30 months)
- Conversions and reversions of repeated QuantiFERON® TB Gold tests between inclusion and month 12 (M12)(ANRS12224 associated study)(12 months)
- Death(60 months)
- Grade 3 or 4 clinical events (including cardiovascular, renal and bone disease) and laboratory test results, as defined by the ANRS classification system of drug-related adverse events(30 months)
- Tuberculosis disease or tuberculosis-related death(30 months)
- Cost-effectiveness of each trial arm in the short- and long-term(30 months)