Randomized, Non-inferiority Trial Comparing a Dual Maintenance Therapy Strategy With Dolutegravir + Lamivudine (DTG/3TC) or Atazanavir/Ritonavir + Lamivudine (ATV/r+3TC) Versus the Standard WHO First Line Triple Therapy Tenofovir + Lamivudine + Efavirenz (TDF+3TC+EFV) or Dolutegravir + Lamivudine + Tenofovir (DTG+3TC+TDF) in West and Central African HIV-1 Infected Patients
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 480
- 试验地点
- 5
- 主要终点
- The treatment success, as defined by using the FDA snapshot algorithm
研究概览
简要总结
MODERATO is a phase III, open-label, randomized, multicenter, non-inferiority trial conducted in West and Central Africa (Cameroon, Côte d'Ivoire, Burkina Faso).
HIV-1 infected adults receiving first line ART with TDF+XTC+EFV or DTG+XTC+TDF virologically suppressed will be recruited and followed during 100 weeks.
The objective is to assess the non-inferiority of a strategy consisting of switching to a dual maintenance therapy (DTG+3TC or ATV/r+3TC), comparing to WHO standard first line regimen (TDF+3TC+EFV or DTG+3TC+TDF), in terms of virological success at 96 weeks
详细描述
In HIV-1 infected adults receiving first line ART with TDF+XTC+EFV or DTG+XTC+TDF virologically suppressed (viral load < detection limit of the technique used) for at least two years: to assess the non-inferiority of a strategy consisting of switching to a dual maintenance therapy (DTG+ 3TC or ATV/r+3TC), comparing to WHO standard first line regimen (TDF+3TC+EFV or DTG+3TC+TDF), in terms of virological success at 96 weeks, in Cameroon, Côte d'Ivoire and Burkina Faso.
This is a trial including two strategies (dual maintenance therapy and triple reference therapy) and three ART regimens (DTG+3TC and ATV/r+3TC used in the maintenance strategy and TDF+3TC+EFV/ DTG+3TC+TDF used in the reference strategy).
The primary analysis will compare the two strategies. Secondary analyses will compare the three ART regimens two by two.
In order to make these secondary analyses possible, participants will be randomly assigned, at inclusion, to each of the three ART regimens (arm 1: DTG+3TC; arm 2: ATV/r+3TC; arm 3: TDF+3TC+EFV / DTG+3TC+TDF). The maintenance strategy will include arm 1 and 2. The reference strategy will include arm 3
Number of participants : 480 (160 in each ART regimen, ie 320 in the dual maintenance therapy strategy and 160 in the triple therapy reference strategy)
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
- •HIV-1 infection
- •Age of legal majority
- •CD4 > 200 cells/mm3 at pre-inclusion
- •Start first-line ART with non-nucleotide reverse transcriptase inhibitors including TDF+XTC+EFV for at least two years without a past history of virological failure, OR
- •Be on TDF+XTC+EFV for at least two years then DTG+XTC+TDF without a past history of virological failure, OR
- •Be on DTG+XTC+TDF (1st line regimen) for at least two years without a past history of virological failure
- •Absence of past history of virological failure (viral load above the threshold corresponding to the test used); two blips between 50 and 200 copies/ml are allowed.
- •At least 2 consecutive HIV-1 RNA < 50 copies/ml within past 2 years, including HIV-1 RNA at pre-inclusion
- •Women with pregnancy potential are required to use an effective contraceptive method throughout the study follow up.
- •Signed informed consent
排除标准
- •HIV-2 infection or HIV-1+2 infection
- •CD4 nadir <100 cells/mm3
- •Chronic Hepatitis B (HBs Ag positive in the pre-inclusion balance)
- •Ongoing active Tuberculosis
- •Ongoing severe opportunistic infection
- •Ongoing chemotherapy or immunotherapy
- •Grade > 2 hemoglobin, neutrophil or platelet disorder
- •ALT≥ 3 times the upper limit of normal value
- •Creatinine clearance < 50 ml/min (CKD-EPI)
- •Allergy to a trial drugs or drug component
- •Ongoing pregnancy or Refusal of contraception
- •Patient at risk of non-compliance
- •Ongoing treatment with a drug that should not be associated with one of the drugs used in the study (cf appendix E page 77)
- •Any symptoms or biological findings suggestive of a systemic disorder (renal, hepatic, cardiovascular, pulmonary) or other medical conditions that may interfere with the interpretation of test results or jeopardize the health of patients
研究组 & 干预措施
Arm 1 : Dual maintenance therapy DTG+3TC
干预措施: dolutegravir (Drug)
Arm 1 : Dual maintenance therapy DTG+3TC
干预措施: Lamivudine (Drug)
Arm 2 : Dual maintenance therapy ATV/r+3TC
干预措施: atazanavir boosted with ritonavir (Drug)
Arm 2 : Dual maintenance therapy ATV/r+3TC
干预措施: Lamivudine (Drug)
Arm 3 : Reference triple therapy TDF+3TC+EFV or DTG+3TC+TDF
干预措施: tenofovir + lamivudine +efavirenz or dolutegravir + lamivudine + tenofovir (Drug)
结局指标
主要结局
The treatment success, as defined by using the FDA snapshot algorithm
时间窗: 90 to 102 weeks
Success : The proportion of patients who are still continuing the assigned strategy and whose last available plasma HIV-1 RNA in the the window analysis is \<50 copies/ml at the end of the window analysis. Failure : patients who have discontinued the assigned strategy or whose last available plasma HIV-1 RNA in the window analysis (90 to 102 weeks) is ≥ 50 copies/ml or with no available HIV-1 RNA in the window analysis
次要结局
- Grade 1,2,3 or 4 hepatic liver disorders or abnormalities(Between Day 0 and Week 96)
- Symptoms(Between Day 0 and Week 96)
- Plasma HIV-1 RNA(Between Day 0 and Week 96)
- CD4 lymphocyte(Between Day 0 and Week 96)
- ANRS grade 3-4 overall morbidity(Between Day 0 and Week 96)
- Failure combined endpoint(Between Day 0 and Week 96)
- WHO stage 3-4 morbidity(Between Day 0 and Week 96)
- Creatinine clearance(Between Day 0 and Week 96)
- ANRS grade 3-4 renal morbidity(Between Day 0 and Week 96)
- Adherence to treatment using a self-questionnaire(Between Day 0 and Week 96)
- ARV drug plasma concentrations in participants with treatment failure(Between Day 0 and Week 96)
- Virological success(Between Day 0 and Week 96)
- Virological failure and new resistance mutations(Week 48 and Week 96)
- New HIV-1 drug resistance mutations(Week 48 and Week 96)
- ANRS grade 3-4 hepatic morbidity(Between Day 0 and Week 96)
- Switched back to triple therapy(Between Day 0 and Week 96)
- ANRS grade 3-4 neurologic morbidity(Between Day 0 and Week 96)
- Grade 1,2,3 or 4 renal disorders(Between Day 0 and Week 96)
- Bone mineral density(Between Day 0 and Week 96)
- Life quality(Between Day 0 and Week 96)
- Grade 1,2,3 or 4 CNS disorders(Between Day 0 and Week 96)
- Cost-effectiveness of the 3 ARV strategies(Week 96)