Randomized Clinical Trial to Evaluate the Interest of a Down-scaled Treatment Strategy Using Dual Therapy (Nucleoside Analogs) in HIV Infected Patients Already Being Treated Using Triple Therapy, Who Present With a Successful Virological Control and for Which the HIV Reservoir is Low to Moderate
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 224
- 试验地点
- 16
- 主要终点
- Viral Load at 48 weeks
研究概览
简要总结
In the early 2000s, the "TRILEGE©" study was realized to determine if the reductive anti retroviral strategy from an initial triple therapy (based on a protease inhibitor as the third agent) towards a dual therapy of nucleoside analogs (in particular the association of "zidovudine +lamivudine") for patients infected by HIV and stabilized for at least 3 months at a threshold value of 400 copies/ml, would allow to obtain a well-controlled plasmatic viral load, with an aim to reduce the long-term side effects of the treatment.
The afore mentioned study showed that the reductive anti retroviral strategy was a failure. No study has as yet to revaluate this strategy, in particular in the current context of antiretroviral treatments.
Indeed, modern nucleoside inhibitors (Kivexa®, Truvada®) have extended half-lives as well as a superior intrinsic power as compared to treatments proposed in the initial "TRILEGE©" study. Furthermore, the better quality of current triple therapy (as compared to that used 10 years ago) has lead to substantial viral reservoir reduction.
Currently, a small number of patients is being successfully treated in the long-term (viral load < 20 copies/ml) using nucleoside analog dual therapy. The particular characteristics of these patients have yet to be thoroughly investigated.
The patients concerned were all treated prematurely before ever passing below 200 lymphocytes T CD4/mm3. It occurred that all these patients presented a low viral reservoir as measured by HIV DNA quantification (< 2,7 log copies/106 PBMC).
Therefore, by targeting patients who have (1) a strong immune restoration, (2) a low HIV DNA value and (3) a very good observance, the investigators emit the hypothesis that, reductive anti retroviral strategy that would consist in changing from a conventional triple therapy towards a Nucleoside reverse-transcriptase inhibitors dual therapy, could allow for durable control of viral replication with the concomitant benefice of reduced antiretroviral side effects and cost.
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-1 infected patient
- •Initial TT ARV started above (or equal to) 150 / mm3 LT CD4, and 18 months prior to inclusion in the study
- •Ongoing antiretroviral therapy combining tenofovir + emtricitabine + a 3rd agent (IP / r, IP, NNRTI, II, Inhibitors) with at least one undetectable viral load (CV <50 copies / mL) after introduction of the latter treatment.
- •Patient in virological success: CV <50 copies / mL for at least 12 months, including visit to selection.
- •Absence of previous therapeutic failure: no viral load ≥ 200 copies / mL (after 6 months of treatment) (Except in the case of a justified therapeutic interruption: travel, stock-out ...) and of obtaining success Virologic after introduction of treatment, without concept of genotypic resistance known to the ARVs used.
- •Cellular DNA-HIV <2.7 log copies / 106 PBMC
- •Zenith RNA-HIV <150,000 copies / ml (excluding viral load values during primary infection if it is documented)
- •No genotypic resistance to currently used and known ARVs
- •Patient who has given written informed consent
- •Affiliate or beneficiary of a social security scheme
- •Patient followed on an outpatient basis, age ≥ 18 years.
排除标准
- •Non-compliant patient
- •Subject is pregnant, or lactating, or of childbearing potential and without contraception
- •Active opportunistic infections
- •Major overweight (BMI ≥ 40)
- •Severe renal pathology (creatinine clearance < 30ml/min)
- •Cirrhosis or severe liver failure (factor V < 50%)
- •Prognosis threatened within 6 months
- •Circumstances that may impair judgment or understanding of the information given to the patient
- •Malabsorption syndromes
- •The following laboratory criteria:
- •Serum ASAT,ALAT > 5 x upper limit of normal (ULN)
- •Thrombocytopenia with platelet count < 50.000/ml
- •Anemia with hemoglobin < 8g/dl
- •Polynuclear neutrophil count < 500/mm3
研究组 & 干预措施
triple therapy
Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor) + third agent (boosted protease inhibitor or unboosted protease inhibitor or integrase inhibitor or celsentri or non-nucleoside reverse transcriptase inhibitor).
干预措施: triple therapy (Drug)
dual therapy
Truvada®"245mg":oral administration Tenofovir Disoproxil Fumarate (nucleotide reverse transcriptase inhibitor) + Emtricitabine (nucleoside reverse transcriptase inhibitor)
干预措施: dual therapy (Drug)
结局指标
主要结局
Viral Load at 48 weeks
时间窗: 48 weeks
Percentage of patient having a viral load \< 50 copies/ml in each arm reductive anti retroviral strategy from an original backbone of 2 Nucleoside reverse transcriptase inhibitors (Tenofovir Disoproxil Fumarate+ Emtricitabine) coupled to a third agent, towards a therapeutic strategy containing the backbone therapy alone (Truvada®).
次要结局
- CD 4 level in each arm(48 weeks)
- Change from week 4 in Viral load at 48 weeks(between 4 weeks and 48 weeks)
- Change from day 0 in HIV - DNA at week 48(day 0 and 48 weeks)
- RNA and DNA viral load (sub study)(Time Frame: Week 24 to Week 48)