Use Of Genotypic HIV-1 Tropism Testing In Proviral DNA To Guide CCR5 Antagonist Treatment In Subjects With Undetectable HIV-1 Viremia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 试验地点
- 24
- 主要终点
- Percentage of patients with viral load under 50 copies/mL
研究概览
简要总结
CCR5 antagonists might be an adequate alternative for HIV-1-infected individuals with suppressed viremia who experience antiretroviral-related toxicity. The assessment of HIV-1 tropism in proviral DNA could be helpful to inform in which of these subjects CCR5 antagonists could be efficacious.
详细描述
The assessment of HIV-1 tropism is needed before starting treatment with a CCR5-antagonist. Several phenotypic and genotyping tropism tests have been developed in the recent years. Phenotypic assays (i.e. TrofileTM and ES-TrofileTM) have been used.in most clinical trials. Genotypic tropism testing, however, is easier, cheaper and faster than phenotypic methods, and can be performed in a local HIV laboratories.
Viral RNA amplification is difficult in subjects with HIV-1 RNA levels <500-1000 copies/mL. In these cases, the optimal source of genetic material is peripheral blood mononuclear cell (PBMC)-associated proviral DNA. Whereas genotypic tropism testing in proviral DNA is technically feasible, it has not been validated as a tool to predict sustained virological response to CCR5-antagonist therapy in subjects with undetectable viremia.
As of today, maraviroc is the only CCR5-antagonist approved for HIV treatment. It has few drug interactions and a good security profile, particularly in terms of lipid and glucose metabolism. Therefore, it might be an adequate alternative for HIV-1-infected individuals with suppressed viremia who experience antiretroviral-related toxicity or metabolic problems.
This study will evaluate 48-week virological outcomes in aviremic subjects with an R5 virus by proviral genotypic tropism testing who switch the "third drug" of their regimen to maraviroc.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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
- 否
入选标准
- •HIV-1 infected patients.
- •Age 18 or more.
- •Antiretroviral treatment containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) plus 1 Non-nucleoside reverse-transcriptase inhibitor (NNRTI) or 1 protease inhibitor (PI) or 1 integrase inhibitor (ININ)
- •Patients receiving stable antiretroviral treatment for at least 6 months.
- •Viral load under 50 copies/mL in the last 6 months
- •Patients with CCR5 tropism based in V3 genotyping in proviral DNA using the G2P with a false positive rate of 10% interpretation method.
- •A change of treatment is needed due to toxicity / tolerability problems with the 3rd drug (PI, NNRTI or ININ), according to investigator criteria.
- •An antiretroviral regimen containing a CCR5-antagonist is suitable for the patient (physician criteria).
- •Voluntary written informed consent.
排除标准
- •Pregnancy or breast-feeding.
- •Patient previously treated with maraviroc.
- •Patients with documented resistance to maraviroc or any other drug considered for the new ARV regimen.
- •Viral failure in the moment of inclusion.
- •Bad adherence history or anticipated (investigator criteria).
研究组 & 干预措施
Change of 3rd drug to maraviroc
Change of PI, NNRTI or integrase inhibitor to CCR5 antagonist (maraviroc)
干预措施: Unique (Drug)
结局指标
主要结局
Percentage of patients with viral load under 50 copies/mL
时间窗: Week 48
次要结局
- Time to loss of virological response (TLOVR) < 50 copies/mL(Up to week 48)
- Time to loss of virological response (TLOVR) < 200 copies/mL(Up to week 48)
- Percentage of patients without confirmed virological failure.(Up to week 48)
- Proportion of patients treated with maraviroc with viral load under 50 copies/mL(Week 48)
- Level of X4 viruses by detected by population sequencing.(Week 48)
- Level of X4 viruses by detected by deep sequencing.(Week 48)
- High-resolution assessment of virus diversity and X4 level using deep sequencing(In case of virological failure (week 12 up to virological failure))
- Median change of total cholesterol.(From baseline to week 48.)
- Median change of HDL cholesterol.(From Baseline to week 48.)
- Median change of LDL cholesterol.(From Baseline to week 48.)
- Time to treatment discontinuation, overall, and due to factors other than loss of virological response(Up to week 48)
- Association between pre-treatment level of X4 viruses detected by deep sequencing at screening and virological response to maraviroc based therapy at week 48.(Week 48)
- Median change of triglycerides(From Baseline to week 48.)
- Median change of AST serum levels.(From Baseline to week 48.)
- Median change of ALT serum levels.(From Baseline to week 48.)
- Median change of alkaline phosphatase serum levels.(From Baseline to week 48.)
- Median change of total bilirubin serum levels.(From Baseline to week 48.)
- Cumulative number of adverse events(Week 48)
- Cumulative number of grade 3-4 adverse events(Week 48)
- Proportion of patients withdrawn from the study and reason for study withdrawal(Up to week 48)