IGHID 11526 - The Compartmental Biology of HIV in the Male Genital Tract
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Tenofovir Diphosphate
研究概览
简要总结
Male participants taking tenofovir-emtricitabine (TDF/FTC) will provide semen and blood samples which will be analyzed to better understand the pharmacology of antiretroviral therapy in the male genital tract.
详细描述
8 HIV positive men taking TDF/FTC and 8 HIV negative men taking TDF/FTC as pre-exposure prophylaxis will provide multiple semen and blood samples during a 48-hour inpatient visit. 8 HIV positive men taking TAF (tenofovir alafenamide) will provide multiple semen and blood samples during a 48-hour inpatient visit.
Participants will take part in the study for approximately two months. After the screening visit, there is one 2 day overnight visit for intensive PK/PD (pharmacokinetic/pharmacodynamic) sampling. The investigators will study drug concentrations and intracellular endogenous nucleotide concentrations (dATP and dCTP) in seminal plasma and (where appropriate) seminal cells.
Samples will be analyzed through the use of novel laboratory methods to determine the seminal plasma and seminal cell concentrations of tenofovir and emtricitabine. New technologies will be used to better understand compartmental and intracellular antiretroviral pharmacology of nucleoside/tide reverse transcriptase inhibitors. Pharmacokinetic modeling will be used to estimate the primary outcomes.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Born male between the ages of 18 and 60
- •HIV positive taking TDF/FTC (and a third drug) as treatment; or HIV negative men receiving TDF/FTC as pre-exposure prophylaxis; HIV positive men taking tenofovir alafenamide
- •if on routine treatment must have been taking medication for at least 3 months and adherence to medication as assessed by blood plasma HIV RNA less than 50 copies per mL.
- •documentation of at least 80% adherence to antiretroviral (ART) regimen, through clinician or self-report, with no missed doses in the 3 days prior to the inpatient visit.
- •willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurologic disease that would pose unnecessary risk or interfere with study results.
- •unwilling or unable to abstain from sexual activity 72 hours prior to overnight sampling visit
- •unlikely to remain on current drug regimen during study period
- •anemia that precludes blood donation
- •unable to provide semen specimen
- •current receipt of other medications that may affect endogenous nucleotide concentrations, such as additional HIV nucleoside reverse transcriptase inhibitors, ribavirin, or adefovir
结局指标
主要结局
Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Tenofovir Diphosphate
时间窗: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of tenofovir diphosphate, an intracellular metabolite of tenofovir, from peripheral blood mononuclear cells, following a 300mg dose of tenofovir.
Semen Clearance (CL) of Tenofovir
时间窗: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
Samples will be analyzed for drug concentrations at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate clearance from semen from a 300mg dose of tenofovir.
Semen Clearance (CL) of Tenofovir Diphosphate
时间窗: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of tenofovir diphosphate, an intracellular metabolite of tenofovir, from seminal mononuclear cells, following a 300mg dose of tenofovir.
Semen Clearance (CL) of Emtricitabine
时间窗: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate clearance from semen from a 200mg dose of emtricitabine.
Semen Clearance (CL) of Emtricitabine Triphosphate
时间窗: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of emtricitabine triphosphate, an intracellular metabolite of emtricitabine, from seminal mononuclear cells, following a 200mg dose of emtricitabine.
Peripheral Blood Mononuclear Cell (PBMC) Clearance (CL) of Emtricitabine Triphosphate
时间窗: Samples collected at 3, 6, 9, 12, 18 and 24 hours post-dose
Samples will be analyzed for drug concentration at the following time points post dose: 3, 6, 9, 12, 18 and 24 hours, and used to estimate the clearance of emtricitabine triphosphate, an intracellular metabolite of emtricitabine, from peripheral blood mononuclear cells, following a 200mg dose of emtricitabine.
次要结局
- Tenofovir Diphosphate (TFVdp)/Deoxyadenosine Triphosphate (dATP) Ratio in Seminal Mononuclear Cells(Average concentration in a 24 hour dosing interval)
- Emtricitabine Triphosphate (FTCtp)/Deoxyadenosine Triphosphate (dCTP) Ratio in Seminal Mononuclear Cells(Average concentration in a 24 hour dosing interval)
研究者
Julie Dumond, PharmD
Assistant Professor
University of North Carolina, Chapel Hill