NEW ERA STUDY - HIV and Eradication: A Multicenter, Open-label, Non-randomized Trial to Evaluate Treatment With Multi-drug Class (MDC) HAART and Its Impact on the Decay Rate of Latently Infected CD4+ T Cells Incl. Amendment 1.0
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 16
- 主要终点
- Combined Endpoint Including HIV RNA and HIV DNA
研究概览
简要总结
This is a multi-center, open-label, non-randomized proof-of-concept trial. Two cooperating HIV-specialized centres represented by Dr. med. Hans Jaeger and Prof. Dr. Johannes Bogner are planning to perform an IIT (investigator initiated trial) with the goal to eradicate HIV in N=40 HIV-infected patients with either primary infection or chronic infection and successful HAART (Highly Active Antiretroviral Treatment) of several years.
All patients will be started on a multi-drug HAART including two Nucleoside-Reverse-Transcriptase-Inhibitors (NRTI´s), one Protease-Inhibitor (PI), a CCR5-inhibitor and an Integrase-Inhibitor (INI). Decay of viral reservoirs like latently HIV-infected CD4+ T-cells will be monitored over time.
详细描述
- Recruitment and Treatment:
Recruitment will be stratified according to stage of HIV-infection and pre-treatment:
- Stratum I (PHI patients):
Patients presenting with primary HIV infection
- Stratum II (CHR patients):
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For all patients:
- •HIV-infected patient
- •Age greater 18 years
- •No acute AIDS-defining disease or history of AIDS- defining disease
- •CD4-cell nadir above or equal 200 cells/µL
- •Hemoglobin greater 8 g/dl
- •Neutrophil count greater 750 cells/µL
- •Platelet count greater 50.000 cells/µL
- •AST/ALT below 5x upper limit of normal range
- •No evidence for drug intolerability
- •No prior use of an HIV integrase inhibitor or CCR5 antagonist
- •No presence of malignancy (requiring active treatment and malignancy within 5 years prior to enrolment (even if in complete remission)
- •No significant underlying disease (non-HIV) that might impinge upon disease progression or death
- •No history of alcohol or other substance abuse or other condition which in the opinion of the investigator would interfere with the patient compliance or safety.
- •Written informed consent
- •For males and premenopausal females use of acceptable methods of birth control during the entire study and for 6 weeks thereafter
- •No pregnancy (for premenopausal women: negative serum or urine pregnancy test within 48 hours prior to initiating study medications)
- •No breastfeeding
- •For chronically HIV-infected patients (CHI):
- •Continuous plasma viral load below 50 copies/ml for the preceding 36 months under HAART (two or less single viral load blips up to 500 copies/ml are allowed)
- •Stable HAART (for at least 3 months) prior to the Screening visit consisting of 2 NRTI + 1 PI
- •No history of virological failure
- •No documented resistance to PI and NRTI
- •CCR5-tropic virus
- •For patients with primary HIV infection (PHI):
- •Detectable plasma viral load
- •ELISA positive or negative and Western Blot negative or positive with less or equal 2 bands at screening visit
- •No primary resistance to PI´s and NRTI´s
- •CCR5-tropic virus
- •Exclusion criteria:
- •Evidence for drug intolerability or contraindication concerning any drug foreseen for MDC HAART
- •Documented HIV-1 resistance to PI and/or NRTI.
- •CD4 nadir <200/µL
- •Acute AIDS-defining disease or history of AIDS-defining disease
- •CHI: preceding virological failure
- •History of alcohol or other substance abuse or other condition which in the opinion of the investigator would interfere with the patient compliance or safety.
- •Any of the following abnormal laboratory test results in screening:
- •Hemoglobin < 8 g/dL
- •Neutrophil count < 750 cells/µL
- •Platelet count < 50,000 cells/µL
- •AST or ALT > 5x the upper limit of normal
- •Presence of malignancy (requiring active treatment and malignancy within 5 years prior to enrolment (even if in complete remission)
- •Significant underlying disease (non-HIV) that might impinge upon disease progression or death
- •Prior use of any experimental HIV- Integrase-Inhibitor or CCR5-antagonist.
- •Patient is pregnant or breastfeeding, or expecting to conceive (within the duration of the study). Patient is expecting to donate eggs (within the duration of the study). Patient is expecting to donate sperm (within the duration of the study).
- •Contraindications for Maraviroc (Celsentri®) or Raltegravir (Isentress®) according to the respective summary of product characteristics (see also product informations attached to the protocol) (Hypersensitivity to the active substances or any of the excipients).
排除标准
- 未提供
研究组 & 干预措施
PHI-patients
Patients with primary HIV infection (PHI) (see also "Eligibility") are immediately treated with 2 NRTI + 1 PI/r + Maraviroc + Raltegravir
干预措施: PHI-patients (Other)
CHI-patients
Patients with chronic HIV infection (CHI) and with suppressed plasma viral load for at least three years under continuous HAART (2 NRTI + 1 PI/r see also "Eligibility") intensified by Maraviroc + Raltegravir
干预措施: CHI-patients (Other)
结局指标
主要结局
Combined Endpoint Including HIV RNA and HIV DNA
时间窗: Screening, month -3 (= pre-baseline only for CHI-patients), baseline, months 1, 3, 6 and then every 6 months until month 84
The primary outcome measure (i.e. achievement of 'eradication') is a combined endpoint including cell-associated proviral DNA and plasma HIV RNA and is defined as undetectable cell-associated HIV DNA (copies per 10exp6 PBMC (peripheral blood mononuclear cells) and per 10exp6 CD4 cells) for at least 2 years (measurement by the French ANRS Group) combined with plasma viral load \< 50 copies/ml for at least 5 years and undetectable plasma viral load (HIV RNA \< 1 copy/ml, 1-copy assay) for at least 2 years.
次要结局
- Absolute HIV DNA in PBMC(Baseline and at months 1, 3, 6 and then every 6 months until month 84)
- Relative CD4+T Cells(Baseline and at months 1, 3, 6 and then every 6 months until month 84)
- Median Change in HIV DNA in PBMC Over Time(Change from baseline at months 1, 3, 6 and then every 6 months until month 84)
- Median Change in CD8+CD38+T Cells Over Time(Change from baseline at months 1, 3, 6 and then every 6 months until month 84)
- HIV RNA <50 Copies/ml (Proportion)(Baseline and at months 1, 3, 6 and then every 6 months until month 84)
- Mean Change in HIV DNA in PBMC (Month 36 and Month 84)(Change from baseline at months 36 and 84)
- Median Change in CD8+T Cells Over Time(Change from baseline at months 1, 3, 6 and then every 6 months until month 84)
- Median Change in CD4+T Cells Over Time(Change from baseline at months 1, 3, 6 and then every 6 months until month 84)
- Mean Change in HIV DNA in CD4+T Cells (Month 36 and Month 84)(Change from baseline at months 36 and 84)
- Median Change in Relative CD4+T Cells Over Time(Change from baseline at months 1, 3, 6 and then every 6 months until month 84)
- Absolute HIV DNA in CD4+T Cells(Baseline and at months 1, 3, 6 and then every 6 months until month 84)
- CD4+/CD8+ Ratio(Baseline and at months 1, 3, 6 and then every 6 months until month 84)
- Absolute CD8+T Cells(Baseline and at months 1, 3, 6 and then every 6 months until month 84)
- Absolute CD4+T Cells(Baseline and at months 1, 3, 6 and then every 6 months until month 84)
- Median Change in HIV DNA in CD4+T Cells Over Time(Change from baseline at months 1, 3, 6 and then every 6 months until month 84)
- Median Change in CD4+/CD8+ Ratio Over Time(Change form Baseline at months 1, 3, 6 and then every 6 months until month 84)
- Absolute CD8+CD38+T Cells(Baseline and at months 1, 3, 6 and then every 6 months until month 84)