A Randomized Multicenter Study With Non-inferiority Hypothesis, Comparing the Availability to Maintain a Complete Viral Suppression by a Monotherapy of Darunavir/r to a NRTI Containing Regimen Including Darunavir/r, in HIV-1 Infected Patients With Previous Prolonged Complete Viral Suppression. ANRS 136 MONOI
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 225
- 试验地点
- 1
- 主要终点
- Proportion of patients with virological success, the virological failure is defined as 2 consecutive plasma viral load measurements greater or equal to 400 cp/ml within 2 weeks at W48
研究概览
简要总结
The purpose of this study is to evaluate whether a monotherapy of boosted darunavir is able to maintain the virological success until 48 weeks in comparison to a standard therapy 2 INTI + darunavir/r in HIV infected patients with full viral suppression.
详细描述
The chronicity of the disease which will require treatment over decades, long-term adverse events associated with standard combined antiretroviral therapy, emphasize the need for simpler, alternative treatment strategies for HIV infection. The goal of antiretroviral therapy in 2006 is the durability of treatment with less toxicity and reduced exposure to drugs. Previous studies have shown that single boosted PI maintenance therapy such as lopinavir (LPV/r), were effective in maintaining virological efficacy. Furthermore, in case of virological failure, limited resistance has been described. darunavir/r, a new PI, has been shown to be highly potent, exhibits a high genetic barrier to resistance and appears to be well tolerated. This study aimed to evaluate whether darunavir/r can represent a potential strategy therapeutic as single therapy in patients who have full virologic suppression At entry, subjects with HIV RNA below 50 cp/ml switch from their current therapy which can be 2 NRTI and IP, 2 NRTI and NNRTI, 3 NRTI to darunavir/r with their 2 NRTIs for 8 weeks (Phase I). If patients remain below 50 cp/ml and has no intolerance to darunavir at week -4, they are included in the phase II and will be randomized either to receive darunavir/r alone or to continue 2 NRTI and darunavir/r for until W48 (Phase II). Patients will be monitored at W4, W8 and then every 8 weeks until W48 for the primary endpoint. To evaluate the durability and safety of this strategy, patients will be followed up to W96
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
- •Confirmed HIV-1 infection.
- •Documented level of HIV-1 RNA at initiation of antiretroviral treatments
- •Prior antiretroviral regimen, including at least 2 NRTIs combined to 1 PI or NNRTI or a third NRTI for at least 18 months prior to study entry.
- •CD4 count of 200 cells per mm3 or greater.
- •Viral load below 400 copies per ml within 18 months prior to entry and below 50 copies per mL at entry.
- •Willing to use acceptable methods of contraception
排除标准
- •Previous virological failure under prior PI-based regimen.
- •Prior therapy in the darunavir.
- •HIV-2 infected patients.
- •Absence of documented level of HIV-1 RNA at initiation of antiretroviral treatments
- •Hepatitis B or C infection within 90 days prior to study entry.
- •Therapies including interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressors at study entry.
- •Serious acute illness requiring systemic treatment or hospitalization in the 14 days prior to study entry.
- •Treatment for an active AIDS defining opportunistic infection within 30 days prior to screening
- •Drug or alcohol use or any dependence that would interfere with compliance.
- •Pregnancy or breastfeeding
研究组 & 干预措施
1
干预措施: Darunavir (Drug)
1
干预措施: ritonavir (Drug)
2
干预措施: Darunavir (Drug)
2
干预措施: ritonavir (Drug)
结局指标
主要结局
Proportion of patients with virological success, the virological failure is defined as 2 consecutive plasma viral load measurements greater or equal to 400 cp/ml within 2 weeks at W48
时间窗: W48
次要结局
- Proportion of patients with virological success between W48 and W96,(W96)
- Proportion of patients with HIV-1 RNA below 50 copies/mL, between 50 to 400 copies/mL and > 400 copies/ml from D0 to W96,(W96)
- Time to virologic failure,(between W0 and W96)
- PI genotypic resistance mutations occurring during the follow-up(between W0 and W96)
- Change in proviral DNA at D0, W48 and W96,(W0, W48 and W96)
- Change in CD4 count from D0 to W96.(D0, W96)
- Change in lipidic and glucidic profile and distribution of fat tissue by DEXA-scan (sub-study in 160 patients enrolled).(W0, W48 and W96)
- Self-reported adherence and symptom self-evaluation.(W0, W4, W24, W48, W96)
- The proportion of patients with HIV RNA below 50 copies/mL in darunavir/r monotherapy arm after resuming 2 previous NRTIs in case of virological failure.(between W0 and W96)
- Search for predictive factors of virological failure (level of proviral DNA, Cmin LPV, …).(between W0 and W96)
- evaluation of the mineral bone density by DEXA-scan (sub-study in 160 patients enrolled).(W96)
- Comparing plasma HIV-1 RNA genotypic resistance with DNA genotypic resistance at entry(D0)
- Quantification of HIV RNA in the genital compartment between D0 and W48 (sub-study with 40 patients enrolled, 20 patients in each arm of strategy).(D0 and W48)
- Incidence of clinical endpoints(W96)
- Modification of treatment strategies and withdrawal of study treatment.(between D0 and W96)
- Tolerance of Darunavir (Grade 3 and 4 laboratory abnormalities and signs and symptoms).(between D0 and W96)