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临床试验/NCT04448158
NCT04448158已完成不适用

Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy

Association de Recherche en Virologie et Dermatologie1 个研究点 分布在 1 个国家目标入组 79 人开始时间: 2020年7月1日最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
发起方
入组人数
79
试验地点
1
主要终点
Detection of M184V mutation

研究概览

简要总结

In view of the prolongation of patients living with HIV's life expectancy, the question of optimization of ART, which is still a life-long treatment, becomes central. While most patients achieve virological success, their treatments often need to be optimized in order to limit adverse events, drugs interactions and to improve adherence. The switch to dual regimen strategies represent one of the approaches for treatment optimization.

Circulating HIV-1 resistant variants can be archived in viral reservoirs, where they can persist for an unknown duration and reemerge in case of therapeutic selective pressure.

There is a need to assess the dynamic of archived Drug resistance associated mutations (DRAMs) clearance in cell-associated HIV DNA after a long period of virological control, in the perspective of ARVs recycling.

The investigators postulate that it could be interesting in the future to recycle ARV drugs (that where classified as "resistant" in the past) in subsequent regimen. The question is particularly important for 3TC/FTC for subsequent new regimen and for the use of dual regimen (disappearance of M184V).

Thus, the investigators propose a retrospective, longitudinal analysis on blood-cell-associated HIV-1 DNA samples in order to investigate by Sanger and Ultra Deep Sequencing the dynamics of decay and persistence of DNA HIV-1 variants harboring key drug resistance-associated mutations to NRTIs, in particular M184V, in patients with sustained virological control for at least 5 years under effective ART.

研究设计

研究类型
Observational
观察模型
Case Only
时间视角
Retrospective

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • HIV-1 infected
  • Age ≥ 18 years
  • Genotypic resistance test performed at time of failure and harboring at least M184V
  • Fully suppressed HIV viral load for at least 5 or 10 years.
  • Triple therapy or 2 drug regimen during the entire follow-up
  • Availability of at least 1 stored whole blood sample /year

排除标准

  • No genotypic resistance test available at time of failure.

结局指标

主要结局

Detection of M184V mutation

时间窗: One measure per year

The persistence of M184V resistance mutation is defined by the detection of this mutation in 2 consecutive samples by Sanger and by a percentage of this mutation \> 1% in 2 consecutive samples by UltraDeep Sequencing. The clearance of M184V is defined by the detection of this mutation by Sanger in a sample and the absence in the subsequent sample or a percentage of this mutation \> 1% in a sample and a percentage \< 1% in the subsequent sample.

Percentage of M184V mutation

时间窗: One measure per year

Percentage detected by UltraDeep Sequencing

次要结局

未报告次要终点

研究者

发起方
Association de Recherche en Virologie et Dermatologie
申办方类型
Other
责任方
Sponsor

研究点 (1)

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