Virological and Immunological Assessment in HIV Positive Participants on 2DR Versus 3DR in a Prospective Randomized Controlled Switch Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 134
- 试验地点
- 1
- 主要终点
- Difference in amount of intact replication-competent HIV-1 sequences in CD4 cells between 2 regimens
研究概览
简要总结
The aim of this study is to monitor virological and immunological markers in participants who are switching from a classic triple drug regimen (3DR) to dual therapy (2DR). We aim to monitor whether this has an influence on different parameters such as severity of HIV disease (evaluated by viral load and viral reservoir size), presence of non-AIDS related health complications, impact the phenotype and function of the immune system.
By conducting this study we want to assess whether switching from 3DR to 2DR implies an increased risk for 'subclinical' failure. We especially want to make sure that this switch does not increase the HIV reservoir, does not increase inflammation or immune exhaustion in patients living with HIV and that it can be considered as a safe long term alternative for the classic 3DR.
The primary objective is to demonstrate non inferiority at W48 of the 2DR DTG/3TC (Dovato) regimen compared to BIC/TAF/FTC (Biktarvy) in terms of the amount of intact replication competent HIV sequences with a non-inferiority margin of 12% quantified by the fraction intact HIV viral sequences quantified by an intact proviral DNA assay, present in blood CD4 cells.
详细描述
In HIV care we have been facing a paradigm change over the last years, reaching an ultimatum with the reimbursement of a 2DR regimen both in naïve as in switch patients.
The rationale behind dual therapy is interesting, namely lower cost, less side-effects, more preserved treatment options, less interactions.
However, from a patient and clinician's perspective this requires a paradigm change after an era of successful treating patient with 3DR.
In the past 2DR and even 1DR treatments have been proposed as an alternative for 3DR, however results were often disappointing and these regimens were only suitable for a selection of patients, often requiring intensification of follow-up.
Recently dual therapy with integrase inhibitor dolutegravir has shown very promising results both in switch (TANGO study) with no virological failure related to this regimen over 48 weeks and in naïve patients (GEMINI study) with no resistance mutations at 96 weeks. Moreover, time to undectability was statistically not different from the 3DR group and the small amount of data available on in depth analysis of the reservoir and immunological parameters were reassuring.
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
- •Age = or >18 years.
- •Ability and willingness to provide written informed consent.
- •Ability to attend the complete schedule of assessments and patient visits.
- •Ability and willingness to have blood samples collected and stored indefinitely and used for various research purposes.
- •HIV RNA < 50 copies/mL for at least 3 months on a 2nd generation INSTI based regimen.
- •Females of childbearing potential should be on effective contraception
排除标准
- •Current presence of opportunistic infection (AIDS defining events as defined in category C of the CDC clinical classification).
- •Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (seroconversion= HBV antigen or viral load negative and positive HBV surface antibody).
- •Evidence of active HCV infection: HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry.
- •Pregnancy or breastfeeding.
- •Patients unable to understand the study protocol or any other condition that in the investigator's opinion may compromise compliance with the study protocol
- •Decompensated liver cirrhosis (Child-Pugh B/C)
- •Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones)
- •Psychiatric and psychological disorders, which in the opinion of the investigator, will interfere with the trial conduct or safety of the participant.
- •Previous participation in a trial evaluating an immune modulating agent.
- •Active drug or alcohol use/addiction such that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- •Treatment failure on an integrase inhibitor containing regimen and reported baseline resistance
- •Creatinine Clearance <50
- •Tuberculosis treatment
- •Documented M184V
- •Previous virological failure >200 copies/mL on NRTI
- •Subjects with history or presence of allergy to any of the study drugs or their components
- •ALT >5 times the ULN, OR ALT >3xULN and bilirubin >1.5xULN (with >35% direct bilirubin)
研究组 & 干预措施
Dovato
We aim to include 134 adult HIV-infected patients with HIV RNA < 50 copies/mL for at least 3 months on any stable 2nd generation integrase based triple therapy antiretroviral regimen. Patients will be randomized 1:2 to switch to or stay on the triple regimen BIC/TAF/FTC (Biktarvy) (N=45) or to switch to the dual regimen DTG/3TC (Dovato) (N=89).
干预措施: Dual versus triple therapy in treatment of HIV-1 infection. (Drug)
Biktarvy
We aim to include 134 adult HIV-infected patients with HIV RNA < 50 copies/mL for at least 3 months on any stable 2nd generation integrase based triple therapy antiretroviral regimen. Patients will be randomized 1:2 to switch to or stay on the triple regimen BIC/TAF/FTC (Biktarvy) (N=45) or to switch to the dual regimen DTG/3TC (Dovato) (N=89).
干预措施: Dual versus triple therapy in treatment of HIV-1 infection. (Drug)
结局指标
主要结局
Difference in amount of intact replication-competent HIV-1 sequences in CD4 cells between 2 regimens
时间窗: 48 weeks
The primary objective is to demonstrate non inferiority at W48 of the 2DR DTG/3TC (Dovato) regimen compared to BIC/TAF/FTC (Biktarvy) in HIV-1 infected individuals in terms of the amount of intact replication-competent HIV-1 sequences with a non-inferiority margin of 12% quantified by the fraction intact HIV viral sequences quantified by the intact proviral DNA assay (IPDA), present in blood CD4 cells.
次要结局
- Quantification of D-Dimers(240 weeks)
- Quantification of soluble cluster of differentiation 27 (sCD27)(240 weeks)
- Quantification of soluble cluster of differentiation 40 (sCD40)(240 weeks)
- Full length sequencing of the virus(240 weeks)
- Quantification of interleukin-6 (IL-6)(240 weeks)
- Quantification of high-sensitivity C-reactive protein (hs-CRP)(240 weeks)
- Quantification of Human Leukocyte Antigen - DR isotype (HLA-DR)(240 weeks)
- Quantification of cluster of differentiation 38 (CD38)(240 weeks)
- Quantification of programmed cell death protein 1 (PD-1)(240 weeks)
- Quantification of cluster of differentiation 28 (CD28)(240 weeks)
- Quantification of cluster of differentiation 57 (CD57)(240 weeks)
- Quantification of soluble cluster of differentiation 14 (sCD14)(240 weeks)
- Quantification of CD4/CD8 ratio(240 weeks)
- Incidence of metabolic syndrome(240 weeks)
- Weight/body mass index (BMI) change(240 weeks)
- Waist circumference(240 weeks)
- Insuline resistance(240 weeks)
- Dual-energy x-ray absorptiometry (DXA)(240 weeks)
- FibroScans(240 weeks)
- Switch questionnaire(240 weeks)
- Duplex carotis(240 weeks)
- Quantification of lipoproteine A(168 weeks)