Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Total Doravirine Concentrations in Cerebrospinal Fluid
研究概览
简要总结
Doravirine is a new HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) that has demonstrated a good efficacy and safety profile in clinical trials. It functions by inhibiting viral replication of both wild-type virus and most common NNRTI variants. It is dosed orally once daily and always given in combination with other HIV-1 active agents as part of highly active antiretroviral therapy. Initial pharmacokinetic studies demonstrated not extensive binding to plasma proteins, which may be crucial determinant for penetration to different reservoirs such as the central nervous system (CNS). This study will address two important issues: The pharmacokinetic profile of Doravirine in cerebrospinal fluid (CSF) as well as the maintenance of HIV suppression in CSF. The assessment of concentrations as well as the antiviral activity of new antiretroviral drugs in compartments such as CNS is relevant to avoid HIV-related neurocognitive disorders as well as for future cure strategies. In addition, the role of unbound ARV drug concentrations has been scarcely evaluated.
详细描述
15 asymptomatic, virologically suppressed, HIV infected patients will be offered to switch their antiretroviral treatment to Doravirine+Emtricitabine/TAF. After 4 weeks of treatment all subjects will undergo lumbar puncture and bloods in order to assess CSF and plasma (total and unbound) Doravirine concentrations. HIV RNA also will be assessed. All subjects will complete a follow up visit 4 weeks after
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Asymptomatic, HIV-1 infected individuals ≥ 18 years of age
- •Be on a stable ART continously or ≥3 consecutive months preceding the screening visit. Patients already receiving TAF/FTC+DoravirineC for at least three consecutive months will be eligible.
- •Plasma HIV-1 RNA at screening <40 copies/mL for at least 3 months at the Screening visit.
- •Signed and dated written informed consent prior to inclusion.
- •Subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study.
排除标准
- •Severe hepatic impairment (Child-Pugh Class C)
- •Ongoing malignancy
- •Active opportunistic infection
- •Primary resistance to any of the ARV included in the study or history of virologic failure with risk of resistance selection to any of the study drugs.
- •Any verified Grade 4 laboratory abnormality
- •ALT or AST ≥ 3xULN and/or bilirubin ≥ 1.5xULN
- •Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min
- •Females who are pregnant (as confirmed by positive serum pregnancy test) or breastfeeding.
- •Current treatment with antiaggregant or anticoagulant therapy.
- •History of any neurologic disease/condition/treatment may alter the blood brain barrier permeability.
研究组 & 干预措施
Doravirine + Descovy® TAF/FTC
Doravirine (MK-1439) 100 mg administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) coformulated as single tablet (Descovy® TAF/FTC 25/200 mg) and administered orally once daily during 4 weeks
干预措施: Doravirine (Drug)
Doravirine + Descovy® TAF/FTC
Doravirine (MK-1439) 100 mg administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) coformulated as single tablet (Descovy® TAF/FTC 25/200 mg) and administered orally once daily during 4 weeks
干预措施: Descovy (Drug)
结局指标
主要结局
Total Doravirine Concentrations in Cerebrospinal Fluid
时间窗: 4 Weeks
Total Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF
Total Doravirine Concentrations in Blood Plasma
时间窗: 4 Weeks
Total Doravirine concentrations in blood plasma
Total Doravirine Concentration CSF/Plasma Ratio
时间窗: 4 Weeks
total Doravirine CSF/plasma ratio
HIV-1 RNA in Cerebrospinal Fluid
时间窗: 4 Weeks
Number of patients with HIV-1 RNA cerebrospinal fluid \<40 copies/ml
HIV-1 RNA in Blood Plasma
时间窗: 4 Weeks
Number of patients with HIV-1 RNA in blood plasma \<40 copies/ml
Unbound Doravirine Concentrations in CSF
时间窗: 4 Weeks
Unbound Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF
Doravirine Concentrations in Blood Plasma
时间窗: 4 Weeks
Unbound Doravirine concentrations in blood plasma
Unbound Doravirine Concentration CSF/Plasma Ratio
时间窗: 4 Weeks
Unbound Doravirine CSF/plasma ratio
次要结局
未报告次要终点
研究者
Daniel Podzamczer
PhD: chief of the HIV and STD Unit (Infectious Disease Service)
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia