Multicenter, International, Prospective, Phase III, Randomized, Superiority Trial Comparing Two Maintenance Strategies With Mono or Bi-therapy of Protease Inhibitors With or Without Lamivudine in Virologically Suppressed HIV Patients on Second Line Antiretroviral Treatment Over a Period of 96 Weeks in Africa (Dakar, Bobo Dioulasso, Yaounde)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 265
- 试验地点
- 5
- 主要终点
- Proportion of patients in virological failure
研究概览
简要总结
Multicenter, randomized, superiority trial to evaluate efficacy of a mono or bi-therapy of protease inhibitors with or without lamivudine over a period of 96 weeks. The primary outcome will be the failure rate at 96 weeks. This study will include 260 participants, former participants of the 2LADY trial. It will be carried out in Yaoundé, Bobo Dioulasso and Dakar.
详细描述
Justification: The interest of treating HIV infection with a single molecule has been clear for a long time. Many clinical trials have been testing the efficacy of such a strategy, mainly using a boosted protease inhibitor (PI). Despite the remaining doubts about low level viremia, viral control in reservoirs, durability of the effect, the trials showed attractive results with an absolute increase in the risk of virological failure between 2% and 13% compared to the standard of care and a possible decrease in costs and toxicity.
In resource-limited countries the interest of treatment simplification is even more important: decrease in costs, toxicity (often poorly monitored), number of pills taken per day, etc. In addition, for patients in second line for whom some kind of resistance to NRTI is highly probable, the interruption of the second line NRTI could help to avoid the accumulation of mutations in the RT in the presence of residual low level replication, sparing future treatment options.
The 184 mutation of the retro-transcriptase which causes resistance to lamivudine/emtricitabine seems to hinder viral replication. The persistence of this mutation could eventually facilitate the action of PI monotherapy while protecting patients from further mutations. The choice of viral load (VL) threshold for the diagnosis of failure in resource-limited countries is not easy, the 2LADY trial used in clinical practice, the threshold of 1000 copies/ml which allows genotyping for evidence of mutations. This value will probably be selected as a reference value by the WHO in its next recommendations. To minimize the risk of viral escape and the development of resistances in the MOBIDIP study the threshold of 200 copies/ml has been chosen for the switch to monotherapy and of 500 copies/ml for the definition of failure.
Principal objective: To evaluate the failure rate at 96 weeks of a PI monotherapy with or without lamivudine, in HIV positive patients on second line treatment (ART) for at least 48 weeks, and with a VL of less than 200 copies/ml in Africa (Yaoundé, Bobo Dioulasso, Dakar).
Specific objectives: To evaluate:
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 infection on second line treatment in the 2lady trial for at least 48 weeks
- •VL ≤ 200 copies/ml since at least 6 months
- •No change in ART in the last 3 months previous to the study
- •CD4> 100 cells/ml
- •Signed informed consent
- •Adherence >90
排除标准
- •Previous viral failure (at least 2 consecutive HIV RNA >1000 copies/ml) while receiving a PI
- •Ongoing pregnancy and breast feeding women
- •HBsAg positive patients
- •opportunistic infection or any severe or progressive disease ongoing or treated in the 3 months before screening
- •Subject who in the investigator's opinion is unable to complete the study
- •History or symptoms of HIV encephalopathy
研究组 & 干预措施
monoPI - boosted lopinavir or boosted darunavir
boosted lopinavir (LPV/rtv 200/50 mg 2 tbs BID) or boosted darunavir (DRV 400 mg 2 tbs plus RTV 100 mg QD)
This arm has been stopped on advise of DSMB (approved by Scientific Committee), patients are switched to standard second line triple therapy and followed until the end of the study at week 96.
干预措施: monoPI - boosted lopinavir or boosted darunavir (Drug)
bi therapy - (boosted lopinavir or darunavir) + lamivudine
boosted lopinavir (LPV/rtv 200/50 mg 2 tbs BID) with lamivudine 300 mg QD or boosted darunavir (DRV 400 mg 2 tbs plus RTV 100 mg QD)with lamivudine 300 mg QD
干预措施: bi therapy - (boosted lopinavir or boosted darunavir) + lamivudine (Drug)
结局指标
主要结局
Proportion of patients in virological failure
时间窗: 96 weeks
Number of patients with a treatment failure. Definition of treatment failure: 1) viral load ≥ 500 copies/ml confirmed in 2 samples with 1 month interval, or 2) the reintroduction of the two NRTIs or 3) interruption of the boosted PI.
次要结局
- The Immune response(Between the inclusion and 96 weeks)
- Tolerability(Between the inclusion and 96 weeks)
- The viral resistance(24 weeks from reintroduction NRTI regimen)
- The clinical course of the HIV infection(Inclusion to 96 weeks)
- Assessment neurocognitive functions(96 weeks)
- virological response(96 weeks)
- Virological response(48 weeks)
- Treatment failure after reintroduction of the baseline NRTI backbone regimen(24 weeks from reintroduction NRTI regimen)
- Assessment of the adherence(96 weeks but an average of mesures of each visits)
- Changes in anthropometric measures(between the inclusion and 96 weeks)