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临床试验/NCT00808002
NCT00808002已完成3 期

Efficacy of Treatment Intensification With Maraviroc on HIV-1 Viral Latency in Recently Infected Hiv-1 naïve Patients Starting Raltegravir Plus Tenofovir/Emtricitabine.

Germans Trias i Pujol Hospital2 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2009年2月最近更新:
适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
已完成
入组人数
30
试验地点
2
主要终点
Change at 48 weeks in the slope of decay of integrated and unintegrated viral DNA in PBMCs.

研究概览

简要总结

The intensification with maraviroc in recently HIV-1-infected patients of a preferred gold-standard triple therapy composed of raltegravir plus tenofovir/emtricitabine could accelerate the decay of the HIV-1 reservoir in latently infected cells established early in HIV-1 infection.

This could provide further insight into this area, decrease the size of latent reservoir, and translate into clinical benefits for patients.

详细描述

A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite continuous highly active antiretroviral therapy (HAART). This is likely to represent the major barrier to virus eradication in patients on successful combination antiretroviral therapy.

The majority of the viruses in the latent reservoir use CCR5 receptor during entry.

More recently, clear evidences for decay of this HIV-1 reservoir in patients who initiated antiretroviral therapy early in infection have been demonstrated. The treatment of acute infection may set the stage for subsequent attempts at eradication. To achieve this, more potent antiretroviral therapy and/or more potent antilatency therapies may be needed.

In contrast to previous antiretroviral drugs, maraviroc does not need to cross the cell membrane, nor does not require intracellular processing in order to exert its activity. In addition, there is no cross-resistance between entry inhibitors and agents that act on intracellular targets.

Maraviroc has demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested. Maraviroc could thus fulfil the requirements for an optimal candidate for treatment intensification in HIV-1 infected patients with a recent HIV-1 infection.

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 99 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • HIV-1 infected adults (>=18 years old).
  • No previous antiretroviral therapy for more than 2 weeks.
  • HIV-1 infection documented in the past 6 months by a previous negative ELISA test, or a documented clinical acute seroconversion in the past 6 months.
  • CCR5-tropism confirmed at screening.
  • Voluntary written informed consent.

排除标准

  • Pregnancy or fertile women willing to be pregnant.
  • Active substance abuse or major psychiatric disease.
  • Presence of NRTI mutations in the screening genotype.

研究组 & 干预措施

1

Experimental

From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD

干预措施: Raltegravir (Drug)

1

Experimental

From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD

干预措施: Maraviroc (Drug)

1

Experimental

From Baseline to Week48: Raltegravir BID + Tenofovir/Emtricitabine QD + Maraviroc BID From W48 to W72: Raltegravir BID + Tenofovir/Emtricitabine QD

干预措施: Tenofovir/Emtricitabine (Drug)

2

Active Comparator

Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine

干预措施: Raltegravir (Drug)

2

Active Comparator

Start ARV treatment with : Raltegravir BID + Tenofovir/Emtricitabine

干预措施: Tenofovir/Emtricitabine (Drug)

结局指标

主要结局

Change at 48 weeks in the slope of decay of integrated and unintegrated viral DNA in PBMCs.

时间窗: BL, W2, W4, W12, W24, W48

次要结局

  • Fibrosis markers in ileum biopsy and PBMC(W48)
  • Plasmatic inflammation biomarkers(BL, W2, W4, W12, W48, W60)
  • Decay of residual HIV-1 replication under maraviroc intensification assessed by an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL.(BL, W2, W4, W8, W12, W24, W36, W48)
  • Blips during the study (viral load >50 copies/mL, preceded and followed by determinations <50 copies/mL in previous and posterior controls).(From Baseline to W48)
  • Relationship between maraviroc and/or raltegravir plasma concentrations and change in the slope of decay of integrated viral DNA in PBMCs(W12, W24, W48)
  • HIV-1 specific CTL responses(BL, W24, W48, W60, W72)
  • HIV-1 RNA below 50 copies/mL at 48 weeks.(W48)
  • Change in the lymphocyte activation marker HLADR+CD38+ from baseline to week 48.(BL, W4, W12, W24, W48, W60, W72)
  • RNA, DNA and viral p24 associated to cells in ileum biopsy and PBMC(W48)
  • Lymphocyte activation marker HLADR+CD38+ in ileum biopsy and PBMC(W48)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Dr . BONAVENTURA CLOTET

Dr. Bonaventura Clotet

Germans Trias i Pujol Hospital

研究点 (2)

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