Phase IV, Randomized, Open Label, Crossover, Intervention Trial to Investigate the Effect of the Switch of Lopinavir/Ritonavir to Raltegravir on Endothelial Function, Chronic Inflammation, Immune Activation and HIV Replication <50 Copies/ml
试验速览
- 阶段
- 4 期
- 发起方
- UMC Utrecht
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Change in flow mediated dilatation (FMD) of the brachial artery
研究概览
简要总结
Treatment with HIV-infection with protease inhibitors is associated with high blood lipids and higher chance for cardiovascular complications. The RASSTER study aims to investigate the effect of switching the protease inhibitor lopinavir/ritonavir to raltegravir on vessel wall function and inflammation,and activation of the immune system. we hypothesize that with this intervention these parameters will improve. Since decreased vessel wall function and inflammation are initial steps in the process of atherosclerosis, it is important to know this data when treating HIV-infected patients.
详细描述
Fixed dose combination lopinavir/ritonavir (LPV/r) is a widespread used antiretroviral drug belonging to the class of protease inhibitors (PIs). PIs are associated with an increased risk of myocardial infarction. However, data is available suggesting increased levels of plasma lipids are not the sole explanation for this observation. Treatment with LPV/r might lead to a decrease of endothelial function as well, thus explaining the increased risk of myocardial infarction besides increased plasma lipids. Raltegravir is a registered antiretroviral drug with no known cardiovascular side effects. We hypothesize that switching LPV/r to raltegravir in HIV-infected patients with suppressed plasma viral load (<50 copies/ml) will lead to an improvement of endothelial function.
Objective
- First, to assess the effect of the switch of lopinavir/ritonavir to raltegravir on endothelial function.
- Second, to assess the effect of the intervention mentioned above on markers of endothelial function; immune activation; chronic inflammation; and, on plasma HIV-RNA below the cut-off of 50 copies/ml.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Age ≥ 18 years
- •HIV-1 infection
- •Treatment with antiretroviral regimen containing lopinavir/ritonavir for at least the previous 3 months
- •No other protease inhibitors besides lopinavir/ritonavir in antiretroviral regimen
- •Subjects must have a minimum period of viral suppression (plasma HIV-RNA < 50 copies/ml) of 6 months
- •Subjects will not have a history of virological failure on antiretroviral therapy
- •Results of previous resistance testing allowing replacement of lopinavir/ritonavir by raltegravir
- •CD4+ cell count > 200 cells/µL
- •Signed informed consent
排除标准
- •Pregnancy
- •Breastfeeding
- •Raltegravir hypersensitivity
- •Treatment of underlying malignancy
- •Renal insufficiency requiring dialysis
- •Acute or decompensated chronic hepatitis (Child-Pugh score C)
- •Modification of antiretroviral regimen in the previous 3 months
研究组 & 干预措施
Raltegravir
At baseline, lopinavir-ritonavir will be switched to raltegravir (cross-over after 8 weeks).
干预措施: raltegravir (Drug)
结局指标
主要结局
Change in flow mediated dilatation (FMD) of the brachial artery
时间窗: week 8, week16
Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks of raltegravir treatment as compared to the control group (treatment with lopinavir/ritonavir)
次要结局
- Change in markers of chronic inflammation(Baseline, week 2, week 4, week 8, week 10, week 12 and week 16)
- Change in markers of immune activation(Baseline, week 2, week 4, week 8, week 10, week 12 and week 16)
- Change in markers of endothelial function(Baseline, week 2, week 4, week 8, week 10, week 12 and week 16)
- Changes in plasma HIV-RNA below 50 copies/ml(Baseline, week 8, week 16)
研究者
S.F.L. van Lelyveld
principal investigator
UMC Utrecht