HIV Reservoir Dynamics After Switching to Dolutegravir in Patients With Two NRTI and a Protease Inhibitor Based Regimen. A Phase IV Open Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 1 of the study compared to day 0
研究概览
简要总结
The purpose of this study is to assess changes in viral reservoir after changing IP/r to dolutegravir in HIV-1 infected patients maintaining undetectable viral load on Antiretroviral Therapy (ART).
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients infected with HIV-1
- •HIV RNA <50 copies / mL for ≥ 1 year with stable ART regimen (≥ 3 months) based on 2 NRTI and PI (Fosamprenavir, atazanavir, lopinavir or darunavir) boosted with 100 mg of ritonavir, or atazanavir (400 mg / d) not boosted with ritonavir, if the 2 NRTIs are abacavir + Lamivudine
- •CD4 + lymphocytes > 200 / mm3
- •Signature of voluntary informed consent
- •A woman may be eligible to enter and participate in the study if:
- •No reproductive potential-defined as post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of getting pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy.
- •It is in childbearing age with a negative pregnancy test on the day of screening and on Day 1 and agrees to use one of the following contraceptive methods to prevent pregnancy:
- •Complete abstinence from penis-vaginal from 2 weeks prior to administration of investigational product, throughout the study, and for at least 2 weeks after discontinuation of all study drugs;
- •Double barrier method (male / spermicidal condom, male condom / diaphragm, diaphragm / spermicide);
- •Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion)
- •Male sterilization confirmed before the entry of the female subject in the study, and that this man is the only sexual partner for women
- •Approved hormonal contraception
- •Any other method with published data show that the expected failure rate is <1% per year.
排除标准
- •Prior virologic failure with an integrase inhibitor
- •Acquired Immune Deficiency Syndrome (AIDS)-defining illness in the last 48 weeks
- •Glomerular filtration rate <50 mL / min, estimated by Chronic Kidney Disease Epidemiology (CKD-EPI) formula
- •Alanine aminotransferase (ALT) ≥5 times the Upper Limit Normal (ULN) or ALT ≥3 X ULN and total bilirubin ≥1,5 ULN (with> 35% direct bilirubin) and / or unstable liver disease (with the presence of ascites, hepatic encephalopathy, hypoalbuminemia, esophageal varices or persistent jaundice) or known biliary disorders excluded Gilbert syndrome or asymptomatic lithiasis) .
- •Positive for hepatitis B (HBsAg +) or need for Hepatitis C Virus (HCV) treatment during the study .
- •Subjects with severe hepatic impairment (Child Pugh Class C).
- •Patients unable to understand the study protocol or any other condition that in the investigator's opinion could jeopardize compliance with the protocol
- •Pregnant or breast-feeding
- •History or presence of allergy to any of the study drugs or their components
研究组 & 干预措施
2 NRTI+ Dolutegravir
22 patients will be treated with 2 NRTI+Dolutegravir 50 mg during 24 weeks
干预措施: Dolutegravir (Drug)
2 NRTI+ Dolutegravir
22 patients will be treated with 2 NRTI+Dolutegravir 50 mg during 24 weeks
干预措施: 2 NRTI (Drug)
2 NRTI + PI
22 patients will be treated with 2 NRTI + PI during 24 weeks
干预措施: PI (Drug)
2 NRTI + PI
22 patients will be treated with 2 NRTI + PI during 24 weeks
干预措施: 2 NRTI (Drug)
结局指标
主要结局
Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 1 of the study compared to day 0
时间窗: 1 week
Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 2 of the study compared to day 0
时间窗: 2 weeks
Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 4 of the study compared to day 0
时间窗: 4 weeks
Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 12 of the study compared to day 0
时间窗: 12 weeks
Changes in mean of Long Terminal repeat (2LTR) in lymphocytes T Cluster of Differentiation 4+ (CD4 +) in peripheral blood obtained at week 24 of the study compared to day 0
时间窗: 24 weeks
次要结局
未报告次要终点