A Pilot Study Evaluating the Maintenance of Viral Suppression After 24 Weeks of Therapeutic Interruption in Chronically HIV-1 Infected Patients With a Low Circulating HIV-DNA Reservoir
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 4
- 主要终点
- Proportion of patients in success
研究概览
简要总结
During the ERAMUNE-01 and -02 studies, the HIV-DNA quantification in the PBMCs (Peripheral Blood Mononuclear Cells) showed showed that some patients had a very low or undetectable reservoir.
Recent studies showed that a low reservoir is associated to a spontaneous virologic control in three specific categories of patients:
- "Elite Controllers": these rare patients are able to spontaneously maintain an HIV-RNA viral load below 50 copies/mL and elevated CD4 counts without any treatment. These patients belong to the B27/B57 haplotypes associated to a reduced risk of HIV contamination but these haplotypes are very rare in the global population (0,3 %)
- "Visconti" patients: early-treated patients, during the primo-infection stage. After 3 to 5 years of treatment, these patients are able to maintain an undetectable HIV-RNA viral load.
- "Salto" patients: these patients are treated a bit later compared to the Visconti cohort, when their CD4 count was above 350 cells/mm3 and their HIV-RNA viral load below 50 000 copies/mL. The follow-up of these patients showed the same capacity of control of the HIV infection for at least 2 years following treatment interruption.
Taking into account these 3 categories of patients which common characteristics is a low reservoir, our objective is to answer the 2 following questions:
- Is it possible to discontinue the treatment in chronically-infected patients with a "normal" immune system and with an undetectable HIV-DNA reservoir?
- Is a low viral reservoir predictive of a treatment-free remission of the HIV infection in chronically-infected patients?
The main objective of the proof-of-concept ERAMUNE-03 trial is to evaluate the proportion of patients in success (i.e. able to maintain a virologic and an immunologic control of the infection) after treatment discontinuation, failure is defined as:
- An HIV-RNA viral load > 400 copies/mL on 2 consecutive tests starting from Week 4
- Or CD4 count < 400 cells/mm3 on 2 consecutive measures starting from Week 4
- Or the onset of an AIDS-related event
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •HIV-1 infected patient
- •CD4 count > 500 cells/mm3
- •CD4/CD8 ratio > 0.9
- •CD4 nadir > 300 cells/mm3
- •HIV-1-RNA plasma viral load < 50 copies/mL under antiretroviral treatment for at least 2 years
- •HIV-1-RNA plasma viral load < 20 copies/mL at baseline
- •HIV-DNA reservoir < 100 copies/million PBMCs
- •Signed fully informed consent form
- •Ability to attend the complete schedule of assessments and patient visits
- •Patient eligible for national social insurance
排除标准
- •Medical history of AIDS-staging event
- •Antiretroviral treatment initiated during primo-infection in absence of anti-HIV antibodies (negative ELISA and Western Blot tests)
- •Change in the antiretroviral treatment combination within the 3 months prior inclusion
- •HIV-2 co-infection
- •History of thrombocytopenia (< 100 000 cells/mm3)
- •Acute neurologic event during primo-infection
- •Chronic and active hepatitis B as defined as positive HBs antigen or positive isolated anti-HBc antibodies
- •Chronic and active hepatitis C as defined as positive anti-HCV antibodies and positive HCV-RNA PCR
- •History of cancer within the 5 years prior inclusion except basocellular cutaneous cancers
- •Comorbidity associated to lifespan < 12 months according investigator's opinion
- •History of auto-immune disease (lupus erythematous, Hashimoto's thyroiditis, ...)
- •Hemoglobin < 7 g/dL, Creatinine clearance < 60 mL/min using the MDRD formula
- •Patients refusal to use a condom for any sexual relationship during the course of the study
- •Refusal from women of childbearing potential to use at least one additional barrier method other than condoms
- •Ongoing pregnancy as documented by a positive blood test performed at screening or later
- •Lactating woman
- •Psychologic unstability or patient state-of-mind incompatible with the participation in the study as evaluated by psychologist at screening
- •Drug or alcohol addiction or abuse
- •Concomitant participation to another trial involving any investigational treatment or device
研究组 & 干预措施
STOP ART
Antiretroviral treatment interruption in 3 successive groups of 5 patients.
"Zero-risk" strategy If after 8 weeks of treatment interruption, at least 1 patient from group 1 does not present any of the failure criteria, patients from group 2 will be included and their treatment interrupted. If after 8 weeks of treatment interruption, at least 2 patients from groups 1 and 2 do not present any failure criteria, patients from group 3 will be included and their treatment interrupted.
干预措施: Antiretroviral treatment interruption (Other)
结局指标
主要结局
Proportion of patients in success
时间窗: Week 24
Success is defined as the maintenance of the controlled viral infection after 24 weeks of therapeutic interruption. Failure is defined as: * An HIV-1-RNA plasma viral load \> 400 copies/mL starting from Week 4 as confirmed by two consecutive measures within 2 to 4 weeks * Or a CD4 count \< 400 cells/mm3 starting from Week 4 as confirmed by two consecutive measure within 2 to 4 weeks * Or the onset of an AIDS-grading clinical event (grade B or C in the CDC classification, version 1993)
次要结局
- Quantitative and qualitative changes from baseline in the HIV-1 reservoir as measured on sorted CD4 lymphocytes subsets(Up to Week 48)
- Changes from baseline in the patient quality of life and in the disease-related symptoms(Up to Week 48)
- Changes from baseline in anti-HIV specific T cells response(Up to Week 48)
- Changes from baseline in immune activation and inflammation markers(Up to Week 48)
- Changes from baseline in CD4 and CD8 lymphocytes counts(Up to Week 48)
- Proportion of patients in virologic success (HIV-1-RNA plasma viral load < 400 copies/mL)(Up to Week 48)
- Changes from baseline in the HIV-1 reservoir as measured by HIV-1 DNA copies per million PBMCs(Up to Week 48)
- Changes from baseline in the proportion of defective HIV-1 DNA(Up to Week 48)
- Changes from baseline in the plasma concentrations of antiretroviral molecules(Up to Week 48)