Early Intensification of Combination Antiretroviral Therapy Including FUZEON® in the Treatment of Progressive Multifocal Leucoencephalopathy During HIV-1 Infection ANRS 125 Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Estimation by the method of Kaplan-Meier of the rate of survival at M12
研究概览
简要总结
Progressive multifocal leucoencephalopathy (PML) is a rare infectious disease of the brain, provoked by the JC virus. It usually occurs in subjects with impaired immune system as during HIV infection. To date, there is no specific antiviral treatment susceptible to cure PML. But it was shown in the setting of HIV-related PML, that combination antiretroviral therapy allows a restoration of the immune system and then might stop the progression of PML.
The objective of this study is to appreciate the supplementary efficiency brought by an association of more powerful antiretroviral molecules including enfuvirtide on the evolution of PML. This research program will involve 30 patients in several centres in France. All the patients who will participate will receive enfuvirtide during 6 months in association with a combination of two or more potent antiretroviral drugs. The total duration of follow-up for a patient will be of 1 year.
详细描述
The aim of this open-label multicentre study is to estimate the effect of an early therapy intensification based on potent antiretroviral combination including enfuvirtide(FUZEON®) on survival in patients with HIV-1-related progressive multifocal leucoencephalopathy (PML).
To demonstrate that the observed rate is significantly superior to 45%, the inclusion of 24 patients is necessary. At last, 30 patients will be recruited towards the risk estimated at 25% of invalid inclusion.
Patients will be included on the following criteria : HIV-1 documented by Western Blot, clinical and radiological (MRI) evidence of active LEMP with clinical evolution (or deterioration) for less than 90 days, documentation of PML diagnosis for less than 30 days at the inclusion, informed consent (patient or confidence surrogate if decision making incapacity). Exclusion criteria will be the following: age less than 18-year-old ; concomitant opportunistic infection of the central nervous system; pregnancy - feeding; co-infection by the HIV2; history of immunotherapy (interleukin 2, alpha-interferon) or of treatment by FUZEON®; history of treatment by cidofovir; contra-indication to receive FUZEON ®.
An independent committee will meet regularly to estimate the validity of PML diagnosis in included patients.
The duration of the treatment by FUZEON® is 6 months in association with a combination of two or more antiretroviral molecules which will be pursued during the next 6 months. These molecules will be chosen according to the past treatment of the patients. A combination including efavirenz, lopinavir/ritonavir, and tenofovir/emtricitabine (under the shape of TRUVADA®) will be proposed to the naïve patients. For the pretreated patient(approximately a quarter of the inclusions), antiretroviral therapy will be chosen in every case on the basis of the therapeutic history and of the viral genotypes of resistance. Such association will contain at least two antiretroviral molecules, issued from two different families among the three following ones (nucleoside inhibitors of the reverse transcriptase, non-nucleoside inhibitors of the reverse transcriptase, protease inhibitors).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •18 years of age and older
- •Have confirmed laboratory diagnosis of HIV infection
- •Presenting with a clinical history of active PML evolving (or continuing to deteriorate) for less than 90 days
- •Diagnosis of PML documented for less than 30 days at the inclusion by cerebral imaging (MRI) AND the absence of another demonstrated etiology AND the detection of JCV DNA in the CSF by qualitative PCR.
- •Signed written inform consent
排除标准
- •Concomitant opportunistic infection of the central nervous system
- •Pregnancy, breast-feeding
- •Co-infection by the HIV2
- •History of immunotherapy including interleukin-2 and alpha-interferon
- •History of treatment by FUZEON® or by cidofovir
- •Contra-indication to receive FUZEON
结局指标
主要结局
Estimation by the method of Kaplan-Meier of the rate of survival at M12
次要结局
- Rate of survival and functional score (Modified Rankin Outcome Scale) at M12
- Evolution of the JC viral load in the CSF and percentage of patients with JC virus clearance of the CSF to M3 and M6
- Evolution of the CD4 and CD8 T cells sub-populations and of the antivirus JC specific T cell responses at M12
- Dosage of the concentration of enfuvirtide in the CSF