Randomized, Open-label and Multicentric Trial Evaluating the Non-inferiority of Antiretroviral Treatment Taken 4 Consecutive Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients With Controlled Viral Load Under Antiretroviral Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 640
- 试验地点
- 120
- 主要终点
- Proportion of patients with therapeutic success at Week 48.
研究概览
简要总结
The trial is an open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a week versus continuous therapy, in HIV infected patients with controlled viral load for at least 12 months and stable antiretroviral treatment since 4 months.
详细描述
Open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a week versus continuous therapy, in HIV infected patients with controlled viral load for at least 12 months and stable antiretroviral treatment since 4 months. The non-inferiority margin (delta) is 5%. The randomization will be stratified according to the family of the third antiretroviral agent (II, PI, and NNRTI). A minimum of 200 patients will be included in the integrase inhibitor strata to provide a sufficient power to assess the efficacy of strategy in this population.
At W48, all patients with virological success in the continuous therapy group will switch to the 4/7 days therapy.
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, coinfection HIV-1/HIV-2 possible
- •Age≥18 years old
- •Current therapy unchanged for the last 4 months
- •Receiving tritherapy with 2 nucleoside reverse transcriptase inhibitor+protease inhibitors or 2 nucleoside reverse transcriptase inhibitor+non-nucleoside reverse transcriptase inhibitors or 2 nucleoside reverse transcriptase inhibitor+integrase inhibitors.
- •Allowed treatment drugs are :
- •1. nucleoside analogs : tenofovir (TDF ou TAF), emtricitabine, abacavir, lamivudine
- •protease inhibitors : lopinavir/r, darunavir/r ou atazanavir/r
- •Non nucleoside reverse transcriptase inhibitors : efavirenz, rilpivirine ou etravirine
- •integrase inhibitors : dolutegravir, elvitegravir/cobicistat ou raltegravir
- •Viruses susceptible to all antiretroviral drugs present in the ongoing tritherapy (AC11-ANRS algorithm).
- •If a genotype is available in the patient medical history; viruses must be susceptible to all ongoing antiretroviral drugs
- •If no RNA genotype available, a genotype will be performed on DNA at screening and will not have to show any resistance to the ongoing antiretroviral drugs
- •Viral load (VL) < 50 cp/mL in the past year, with at least 3 VL measurements including screening; only one episode of viral blip < 200 copies/mL is authorized in the last year
- •CD4 T cells > 250/mm3 at the screening visit
- •Estimated glomerular filtration rate > 60 mL/min (Chronic Kidney Disease - Epidemiology Collaboration method)
- •Transaminases : aspartate aminotransférase et alanine aminotransférase < 3N
- •Haemoglobin > 10 g/dL
- •Platelets > 100 000/mm3
- •For women of childbearing age, negative pregnancy test at screening; agree to use mechanical contraception during the study
- •Social security system coverage
- •Informed consent form signed by patient and investigator
排除标准
- •Infection by HIV-2
- •Chronic and active Viral B Hepatitis with positive antigen HBs
- •Chronic and active Viral C Hepatitis with treatment expected in the next 98 weeks
- •Concomitant treatment using interferon, interleukins, any other immune-therapy or chemotherapy, antivitaminK for patients on ARVT using a booster
- •Concomitant prophylactic or curative treatment for an opportunistic infection
- •All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with study protocol compliance, observance and/or study treatment tolerance
- •Pregnant or breast feeding women
- •Subjects under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship
研究组 & 干预措施
4 days / 7
Patients included in this arm will take their ARV treatment 4 consecutive days per week during 98 weeks
干预措施: Treatment discontinuation (Drug)
7 days / 7
Patients included in this arm will continue their ARV therapy 7 days per weeks during 48 weeks and after W48, they will take their ARV treatment 4 days per week until W98
干预措施: Treatment discontinuation (Drug)
结局指标
主要结局
Proportion of patients with therapeutic success at Week 48.
时间窗: Week 48
To evaluate after 48 weeks the therapeutic success of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, defined by : * absence of virological failure : a measure of the viral load will be done, this measure have to be \< 50 cp/mL. If it's \> 50 cp/mL, a second measure will be done at 2 to 4 weeks apart. If it's still \> 50 cp/mL, it's a virological failure * no discontinuation or modification of the study strategy for more than 30 consecutive days.
次要结局
- Virological success(Week 48 and Week 96)
- Number of virological " blips "(between Week 0 and Week 48, and between Week 0 and Week 96)
- Percentage of patients with a viral load signal detected(between Week 0 and Week 48 and Week 0 and Week 96)
- Frequency of minority resistant variants archived in DNA at Week 0 and their impact on virological failure (2 consecutive VL> 50 copies / mL) and on the acquisition of drugs resistance mutations(Week 0)
- Proportion of patients with therapeutic success at Week 96(Week 96)
- Proportion of patients with acquisition of drugs resistance mutations in case of virological failure detected by Sanger and by next generation sequencing(Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 (if it's necessary))
- Description of the factors associated with virological rebound (viral load >50 cp/mL).(Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 (if it's necessary))
- Evolution of T cluster of differentiation 4 and cluster of differentiation 8 cells count, and T cluster of differentiation 4 /cluster of differentiation 8 ratio(from Week-4 to Week 48 and Week 96)
- Evolution of ultra sensitive viral load and total DNA in the peripheral blood mononuclear cells at Week 0, Week 24, Week 48 and Week 96; evolution of viral genotypic sequence between Week 0, Week 48 and Week 96 (subgroup of 120 patients)(between Week 0, Week 48 and Week 96)
- Evolution of fasting metabolic parameters(until Week 48 and Week 96)
- Evolution of inflammation and immune activation parameters(from Week 0 to Week 24 and Week 48)
- HIV RNA viral load in semen(Week 0, Week 24 and Week 48)
- Residual plasmatic concentrations of the third antiretroviral agent(Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96)
- Residual plasmatic concentrations of tenofovir (TDF or TAF)(Week 0, Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96)
- Residual intracellular concentrations of the third antiretroviral agents(Week 0, Week 24 and Week 48)
- Treatment adherence(Week 0, Week 12, Week 24, Week 36, Week 48, Week 72,and Week 96)
- Quality of life(Week-4, Week 0, Week 48 and Week 96)
- Patient satisfaction(Week 0, Week 12, Week 48 and Week 96)
- Pharmaco-economic aspects of the strategy(Between Week 0 and Week 98)
- Median time to virologic failure(Between week 0 and 98)
- Frequency of grade 3 or more adverse events, adverse effects, drug-modifying adverse events, drug-related adverse events and serious adverse events (SAE)(Between Week 0 and Week 98)
- Patient Quality of life(Week-4, Week 0, Week 48 and Week 96)