A Pilot Study to Assess Virologic Suppression and Immune Recovery With Raltegravir and Lopinavir/Ritonavir and Raltegravir and Emtricitabine/Tenofovir in HIV-1 Infected Treatment-naïve Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Time to Virologic Failure
研究概览
简要总结
A prospective, randomized, open-label pilot study to assess virologic suppression and immunologic recovery associated with a two-drug antiretroviral regimen of Raltegravir and the protease inhibitor lopinavir/ritonavir (LPV/r) and a three drug regimen with Raltegravir and two nRTIs (emtricitabine/tenofovir) in HIV-1 infected treatment-naïve subjects.
Immunology Substudy added to determine the kinetics of recovery of CD4 T cells and subpopulations (regulatory T cell [T regs], TH-17 and TH1) after treatment initiation with Raltegravir based regimens and their relationship with functional CD8 T cells and if Raltegravir containing therapies leads to decreases in markers of gut microbial translocation and of cellular and soluble markers of immune activation.
详细描述
A009 is a prospective, randomized, open-label pilot study to assess virologic suppression and immune recovery rates associated with a two-drug potent antiretroviral regimen of raltegravir and the protease inhibitor lopinavir/ritonavir and a three-drug regimen with raltegravir and two nRTIs (emtricitabine/tenofovir) in treatment-naïve subjects.
HIV-1-infected subjects who are antiretroviral drug-naïve and have plasma HIV-1 RNA levels ≥5000 copies/ml obtained within 30 days prior to study entry will be randomized 1:1 to Raltegravir 400 mg BID + LPV 400 mg/RTV 100 mg BID (Arm A) or Raltegravir 400 mg BID + FTC 200 mg/TDF 300 mg QD (Arm B).
Subjects will have measurements of HIV-1 RNA and CD4+ and CD8+ T-cell counts at pre-entry and entry. The average of these measurements will be used to establish their baseline values. Following entry, subjects will have plasma HIV-1 RNA samples drawn at days 2, 4, 8 and at weeks 2, 4, 8, 16, 24, 32, 40 and 48 and at virologic failure. CD38 expression on CD4+/CD8+ cells and CD38/HLA-DR activation antigen on CD4+ and CD8+ cells and subsets T-cell percentage will be done at entry, day 8 and weeks 4, 8, 24 and at virologic failure by advanced flow cytometry.
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
- •Documented HIV Infection
- •Genotypic resistance without major resistance mutations within 30 days
- •Antiretroviral drug-naïve
- •Screening HIV-1 RNA ≥5000
- •Women of reproductive potential
- •Negative pregnancy test within 48 hours
排除标准
- •Acute or recent HIV-1 infection
- •Currently breast feeding
- •Use of immunomodulators
- •Evidence of major resistance mutations
- •HBsAg positive
- •Acute hepatitis of any etiology or clinically significant liver disease
- •Current imprisonment or involuntary incarceration
研究组 & 干预措施
Raltegravir & Lopinavir/ritonavir
Raltegravir 400 mg tablet and Lopinavir/ritonavir capsule by mouth, every 12 hours for 48 weeks
干预措施: Raltegravir & Lopinavir/ritonavir (Drug)
Raltegravir & emtricitabine/tenofovir
Raltegravir 400 mg tablet bu mouth, every 12 hours for 48 weeks and tenofovir/embritcitabine 200 mg/100 mg table by mouth, once daily for 48 weeks
干预措施: Raltegravir and emtricitabine/tenofovir (Drug)
结局指标
主要结局
Time to Virologic Failure
时间窗: week 24 (up to 48 weeks)
time to virologic failure at week 24 (up to 48 weeks)
Time to Confirmed Virologic Failure
时间窗: weeks
time to confirmed viologic failure at 24 weeks (up to 48 weeks)
次要结局
- Weeks to HIV-1 RNA <200 Copies/ml(from date of treatment start to first week documented viral suppression)
- Change From Baseline CD4+ and CD8+ Cell Counts(Baseline, Weeks 16 and 24)
- Study Medication Tolerability(date started study treatment to first week documented change study treatment up to week 48)
- Study Medication Toxicity-related Discontinuation .(48 weeks)
研究者
Margaret A. Fischl, M.D.
Professor of Medicine, Director AIDS Clinical Research Unit
University of Miami