Effectiveness of a Dual Therapy (Dolutegravir + Lamivudine) on Reduction of the Viral Reservoir, Immune Recovery and Immune Activation Compared With a Triple Therapy (Dolutegravir + Tenofovir Alafenamide/Emtricitabine) in Treatment-naïve HIV-Infected Patients
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- proviral HIV-DNA
研究概览
简要总结
The objective of this study is to clarify whether if starting antiretroviral treatment based on dual therapy (DTG + 3TC) could provide less control of residual HIV replication and, therefore, a detriment on immune activation and inflammation compared to starting with triple therapy, and could worsen the patients' long-term prognosis. For this purpose, the investigator has designed a randomized clinical trial where will assess the immunological recovery (CD4+/CD8+), immune activation, proliferation, senescence and apoptosis in T lymphocytes CD4+ and CD8+ cells by flow cytometry, the immune activation of monocytes/ macrophages and plasma concentrations of various inflammatory mediators by ELISAS, and the thymic function, the cellular reservoir of HIV and the degree of HIV DNA transcription by digital dropped PCR.
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
- •Treatment-naïve HIV-1-infected patients ≥ 18 years of age.
- •Plasma HIV-1 RNA >5000 and <500.000 copies/ml.
- •T lymphocyte CD4+ count in peripheral blood >200/μl.
- •Patients of childbearing age should consent to use a highly effective contraceptive method from 15 days before the time of inclusion of the study until 30 days after the end of it. It is considered a highly effective method:
- •Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of Investigational Product, throughout the study, and for at least 2 weeks after discontinuation of all study medications;
- •Any intrauterine device with published data showing that the expected failure rate is <1% per year (not all intrauterine devices meet this criterion)
- •Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject.
- •Approved hormonal contraception.
- •Any other method with published data showing that the expected failure rate is <1% per year.
- •Signed written informed consent prior to inclusion.
排除标准
- •Acute HIV infection
- •T lymphocyte CD4+ count in peripheral blood ≤ 200/µl
- •Active opportunistic infection.
- •Pregnancy at inclusion or during the follow-up
- •Active hepatitis C and/or B virus co-infection.
- •ALT ≥ 5 times the ULN, or ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin).
- •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).
- •Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
- •Current or past disease that requires the use subsidiary of treatment with corticosteroids, immunomodulatory agents, interferon or chemotherapeutic agents.
- •Any laboratory abnormality grade 3 or 4 according to the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (Annex 3)
- •Concomitant use of drugs with potential major interactions with the prescribed drugs according to the respective full prescribing information.
- •Estimated creatinine clearance <50ml/min.
- •History or presence of allergy to the study drugs or their components
研究组 & 干预措施
Dual Therapy
Dolutegravir plus lamivudine
干预措施: Randomize (Drug)
Triple Therapy
Dolutegravir plus TAF/FTC
干预措施: Randomize (Drug)
结局指标
主要结局
proviral HIV-DNA
时间窗: 48 and 96 weeks
Mean changes in proviral HIV-DNA in PBMCs after 48 and 96 weeks of treatment
次要结局
- Immune Recovery(48 and 96 weeks)
- Monocytes Activation(48 and 96 weeks)
- Immunosenescense(48 and 96 weeks)
- Inflammation(48 and 96 weeks)
- Immune Activation(48 and 96 weeks)
- Viral Reservoir(48 and 96 weeks)
研究者
Luis F. Lopez-Cortes
Principal Investigator
Hospitales Universitarios Virgen del Rocío