A Randomized Prospective Open Label Study of Switching to Raltegravir Based ART Compared to Maintaining Ritonavir Boosted PI-based ART on Liver Fibrosis Progression in HIV-HCV Coinfected Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 3
- 主要终点
- To evaluate the effect of switch on change in liver fibrosis score
研究概览
简要总结
HIV infection exerts a negative impact on the course of HCV infection. Co-infected individuals progress more rapidly to liver fibrosis, cirrhosis and ESLD compared to those infected with HCV alone. Some of the this accelerated fibrosis may be related to longterm chronic toxicity from protease inhibitor based ART.
Hypothesis: Switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI).
详细描述
Primary Objective-To assess if switching from ritonavir boosted-PI based ART regimen to a Raltegravir-based regimen will reduce the rate of hepatic fibrosis progression in HIV-HCV co-infected patients as measured by transient elastography (Fibroscan®) and the AST-to-platelet ratio index (APRI) after 48 weeks of treatment.
Secondary Objectives:
(i) To assess the safety and tolerability of switching from a ritonavir boosted-PI ART regimen to a raltegravir-based regimen for 48 weeks.
(ii) To evaluate hepatic function (liver enzymes) at weeks 0, 2, 4, 8, 12, 24, 36, 48 and 72 post switch.
(iii) To evaluate the effect of switching treatment on control of HIV infection (as measured by HIV viral load and CD4) at weeks 0, 4, 8, 12, 24, 36, 48, and 72 post switch.
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
- •18 years or older
- •Chronic HIV-HCV co-infection (HCV RNA + for at least 6 months and could have had previous HCV treatment).
- •Receiving ritonavir boosted PI-based ART for at least 6 months.
- •APRI score ≥ 1.5 (equivalent to liver biopsy score of ≥ F2) AND/OR Fibroscan > 6.9KPa
- •HIV viral suppression (<50 copies/mL) for at least 6 months.
- •No prior evidence of resistance to raltegravir or co-administered nucleoside backbone.
- •No prior history of virologic failure.
排除标准
- •Clinical evidence of decompensated liver disease (e.g., ascites, esophageal varices, or hepatic encephalopathy hepatoma or hepatocellular carcinoma).
- •Chronic Hepatitis B infection (defined as positive HBsAg or Hepatitis B viral load greater than 10,000 copies/mL).
- •AFP greater than or equal to 200 ng/mL at screening.
- •Known or suspected Wilson's disease, alpha-1-antitrypsin deficiency, celiac disease or other cause of chronic liver disease.
- •Chronic renal insufficiency (eGFR < 20 mL/min) at screening.
- •Pregnancy and planned pregnancy (WOCBP not using adequate contraception).
- •Women who are breastfeeding.
- •Active opportunistic infection (except oral thrush) or neoplasm (except Kaposi's sarcoma, skin cancer, or cancer of the cervix or anus, unless known or suspected liver metastasis).
- •Patients intending to start HCV therapy within the treatment phase (within the year following the baseline visit).
研究组 & 干预措施
ritonavir-boosted protease inhibitor
干预措施: Raltegravir (Drug)
ritonavir-boosted protease inhibitor
干预措施: Ritonavir-boosted protease inhibitor (Drug)
Raltegravir
干预措施: Raltegravir (Drug)
Raltegravir
干预措施: Ritonavir-boosted protease inhibitor (Drug)
结局指标
主要结局
To evaluate the effect of switch on change in liver fibrosis score
时间窗: 48 weeks
Change in fibrosis will be assessed by: 1. Change in Fibroscan® score (kPa) at 48 weeks from baseline 2. Change in log transformed AST-to-platelt ratio (APRI) score at 48 weeks from baseline
次要结局
- To evaluate inflammatory markers associated with liver fibrosis(72 weeks)
- To evaluate effect of switch on hepatic function(72 weeks)
- To evaluate effect of switch on metabolic parameters(72 weeks)
- Immunologic and virologic safety(72 weeks)
研究者
Marina Klein
MD
McGill University Health Centre/Research Institute of the McGill University Health Centre