Multicentric, Non-inferiority, Randomized, Non-blinded Phase 3 Trial Comparing Virological Response at 48 Weeks of 3 Antiretroviral Treatment Regimens in HIV-1-infected Patients With Treatment Failure After 1st Line Antiretroviral Therapy (Cameroon, Burkina Faso, Senegal)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 454
- 试验地点
- 3
- 主要终点
- Number of Patients With Plasma HIV RNA < 50 Copies/mL
研究概览
简要总结
Since the first line antiretroviral (ARV) treatment is now largely accessible in the Sub-Saharian Africa countries, documentation of virological failure, drug resistance patterns and second line treatment evaluation are still to be consolidated in settings where viral load monitoring is not available and non-B HIV subtype is predominant.
This trial aims at evaluating the efficacy and tolerance of 3 different second line treatment strategies: two recommended by WHO combine two non-nucleoside reverse transcriptase inhibitor associated with a ritonavir boosted protease inhibitor (emtricitabine-tenofovir-lopinavir/ritonavir and abacavir-didanosine-lopinavir/ritonavir); the third strategy combines emtricitabine-tenofovir-darunavir/ritonavir and is not yet evaluated in Sub-Saharian Africa. Darunavir has a potentially superior antiviral efficacy, a better tolerance and its single daily administration may facilitate treatment adherence.
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
- •Patient over the age of 18 years at pre-inclusion and monitored under outpatient conditions
- •Documented HIV-1 infection regardless of clinical stage and CD4 lymphocyte count
- •Patient with treatment failure after first-line antiretroviral treatment with a combination including a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors, failure being defined as 2 measurements (at 1 month interval) of plasma HIV RNA levels > 1000 copies/ml after at least 6 months of uninterrupted treatment
- •Adherence (> 80%) to first- line antiretroviral treatment (questionnaire) at pre inclusion
- •Patient agrees not to take any concomitant medication during the trial without informing the investigator
- •Informed consent signed no later than D-15
- •For women in childbearing age: negative pregnancy test at inclusion, with no plan of pregnancy in the coming 12 months and agreeing to use mechanical contraception (with or without hormonal contraception) during the study
排除标准
- •Infection with HIV-2 or HIV-1 groups O or N or HIV1+2
- •Deficiency of the patient, making it difficult, if not impossible, for him/her to take part in the trial or understand the information provided to him/her
- •Participation in any other clinical trial
- •Presence of an uncontrolled, ongoing opportunistic infection or of any severe or progressive disease
- •First-line treatment with a protease inhibitor, abacavir, tenofovir or ddI
- •Ongoing treatment with rifampicin
- •Severe hepatic insufficiency (TP < 50%)
- •ALAT > 3 x ULN
- •Creatinine clearance calculated by Cockcroft formula < 50 ml/min
- •Hb ≤ 8 g/dl
- •Platelets < 50,000 cells/mm3
- •Neutrophiles < 500 cells/ mm3
- •Use of drugs prohibited in the context of this trial (drugs contraindicated by the SCP of the trial drugs) - in the event of tuberculosis or malaria during the trial, a list of authorized medicines and, if necessary, a dose adjustment of the antiretroviral medication will be provided
- •Pregnancy or lactation
研究组 & 干预措施
Arm A
emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
干预措施: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line) (Drug)
Arm B
abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
干预措施: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line) (Drug)
Arm C
emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
干预措施: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation) (Drug)
结局指标
主要结局
Number of Patients With Plasma HIV RNA < 50 Copies/mL
时间窗: 48 weeks
次要结局
- Number of Patients With WHO Stage 3 and 4 HIV Related Events(between baseline and 48 weeks)
- Patients With Plasma HIV RNA < 200 Copies/ml(48 weeks)
- Gain in CD4 Cells Between Baseline and W48(between baseline and 48 weeks)
- Number of Patients Discontinuing Study Treatment(between baseline and W48)
- Tolerance: Gastrointestinal Complains(between baseline and 48 weeks)
- Tolerance: Neuropathies (Grade 1 to 4)(between baseline and W48)
- Tolerance: Equal or Superior to a 25% Reduction in eGFR (Glomerular Filtration Rate)(between baseline and W48)
- Adherence(between baseline and W48)
- Number of Patients With Resistance Mutations(between W12 and W48)
- Development of Metabolic Syndrome(from baseline to week 48)
- Number of Patients With HIV Plasma Viral Load < 50 Copies/ml(Week 24)
- Number of Patients With HIV Plasma Viral Load < 200 Copies/ml(Week 24)