Impact of MK-0518 (Raltegravir) Intensification on HIV-1 Viral Latency in Patients With Previous Complete Viral Suppression
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 3
- 主要终点
- Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs
研究概览
简要总结
An intensification with the HIV-1 integrase inhibitor Raltegravir (RAL) of a stable HAART regimen with persistent HIV-1 viral suppression could increase the slope of decay of the HIV-1 latent reservoir.
详细描述
While highly active antiretroviral therapy (HAART) reduces plasma HIV-1 levels to below the limits of detection with standard assays, replication-competent virus persist in a stable, latent reservoir in resting CD4+ T cells. So, there is a rapid resumption in plasma viremia when therapy is interrupted.
In addition to cellular reservoir, other pharmacologically privileged areas such as the central nervous system and the genital tract might act as additional sources of residual virus in patients with undetectable levels of plasma HIV-1 RNA. There is great current interest in strategies for depleting and eliminating this reservoir.
The antiviral potency of current regimens emerges as an important determinant of complete viral control. In certain patients, the latent reservoir decay can be hastened with treatment intensification.
An intensification with the HIV-1 integrase inhibitor Raltegravir (RAL) of a stable HAART regimen with persistent HIV-1 viral suppression could increase the slope of decay of the HIV-1 latent reservoir. This could provide further insight into this area, decrease the size of latent reservoir, and translate into clinical benefits for patients being simplified to maintenance monotherapy with RAL or in the HIV-1 rebound kinetics and slope after a programmed treatment interruption.
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
- 否
入选标准
- •HIV-1 infected adults (+18 years old).
- •Complete virological suppression (<50 copies/mL) for += 12 months, including at least 3 times during the last year.
- •Patients on HAART regimen including a PI or an NNRTI and at least two nucleotide inhibitors.
- •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 drug-related mutations or any polymorphism or mutation associated to MK-0518 resistance prior to first HAART (only if genotype is available).
研究组 & 干预措施
A
MK-0518 400mg twice a day
干预措施: MK-0518 400mg twice a day (Drug)
结局指标
主要结局
Quantification of integrated and unintegrated viral HIV-1 DNA in PBMCs
时间窗: Basal, week 12, week 24 and week 48
次要结局
- Lymphocyte activation marker CD8+HLADR+CD38+(Basal, week 2, week 4, week 12, week 24 and week 48.)
- Quantification of residual HIV-1 (using an ultrasensitive RT-PCR assay with a lower limit of quantification of 5 copies/mL)(Basal, week 1, week 2, week 4, week 8, week 12, week 24, week 36 and week 48)
- Blips during the study (> 50 copies/mL, preceded and followed by determinations < 50 copies/mL in previous and posterior controls)(Basal, week 4, week 8, week 12, week 24, week 36 and week 48)
- Level of apoptosis in CD4 and CD8 T cells.(Week 48 and week 60)
- Raltegravir plasma trough concentration.(Week 12, week 24 and week 48)