Defining the Rectal Mucosa in Men Who Have Sex With Men at Risk of HIV Infection
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Median Percentage of CD4 Positive T-Cells
研究概览
简要总结
The purpose of this study is to determine whether the use of rectal lubricants can affect how well the medication, Truvada, will work to prevent infection with HIV when someone is exposed to HIV in the rectum.
详细描述
Men who have sex with men (MSM) continue to be disproportionately affected by HIV. The majority of HIV infections among MSM occur through exposure to the rectal mucosa during receptive anal intercourse (RAI). During RAI, many MSM will use lubricants, which can potentially cause mucosal inflammation and damage. A new HIV prevention intervention, called pre-exposure prophylaxis (PrEP), recommends that MSM at risk of HIV infection take a daily anti-HIV medication called Truvada (tenofovir/emtricitabine) which is highly effective. However, it is not known if the use of lubricant during RAI will interfere with the efficacy of PrEP for HIV prevention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •HIV-negative man who reports receptive anal sex with another man in the last 6 months aged 18-49 years
- •Male to female transgender women who are not currently taking hormonal therapy or plan to take hormonal therapy for the duration of the study
- •Not currently taking pre-exposure prophylaxis (PrEP) and no plans to initiate during study
- •Able to provide informed consent in English
- •No plans for relocation in the next 6 months
- •Willing to undergo peripheral blood and rectal biopsy sampling
- •Willing to use study products as directed
- •Willing to abstain from receptive anal intercourse 3 days prior to study visit 2 (4-16 weeks after the screening visit)and 10 days prior to study visit 4 (5-26 weeks after the screening visit)
- •Willing to abstain from receptive anal intercourse for 1 week after study visit 2 (4-16 weeks after the screening visit) and study visit 4 (5-26 weeks after the screening visit)
排除标准
- •History of inflammatory bowel disease or other inflammatory, infiltrative, infectious or vascular condition involving the lower gastrointestinal tract that, in the judgment of the investigators, may be worsened by study procedures or may significantly distort the anatomy of the distal large bowel
- •Significant laboratory abnormalities at baseline visit for rectal biopsies, including but not limited to:
- •Hemoglobin (Hbg) ≤ 10 g/dL
- •Partial thromboplastin time (PTT) > 1.5x upper limit normal (ULN) or international normalized ratio (INR) > 1.5x ULN
- •Platelet count <100,000
- •Any known medical condition that, in the judgment of the investigators, increases the risk of local or systemic complications of endoscopic procedures or pelvic examination, including but not limited to:
- •Uncontrolled or severe cardiac arrhythmia
- •Recent major abdominal, cardiothoracic, or neurological surgery
- •History of uncontrolled bleeding diathesis
- •History of colonic, rectal, or vaginal perforation, fistula, or malignancy
- •History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal or vaginal mucosa, or untreated sexually transmitted disease with mucosal involvement
- •Continued need for, or use during the 14 days prior to enrollment, of the following medications:
- •Aspirin or more than 4 doses of nonsteroidal anti-inflammatory drugs (NSAIDs)
- •Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
- •Any form of rectally administered agent besides products lubricants or douching used for sexual intercourse
- •Continued need for, or use during the 90 days prior to enrollment, of the following medications:
- •Systemic immunomodulatory agents
- •Supraphysiologic doses of steroids
- •Experimental medications, vaccines, or biologicals
- •Intent to use HIV antiretroviral PrEP during the study, outside of the study procedures
- •Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain, discharge, bleeding, etc.)
- •Current use of hormonal therapy
- •Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements
研究组 & 干预措施
Rectal Gel Lubricant
Subjects will insert 5 mL of lubricant in rectum for seven consecutive days
干预措施: Gel lubricant (Device)
Truvada
Subjects will take one Truvada tablet orally for seven consecutive days
干预措施: Truvada (Drug)
Rectal Gel Lubricant + Truvada
Subjects will insert 5 mL of lubricant in rectum and take one Truvada tablet orally for seven consecutive days
干预措施: Truvada (Drug)
Rectal Gel Lubricant + Truvada
Subjects will insert 5 mL of lubricant in rectum and take one Truvada tablet orally for seven consecutive days
干预措施: Gel lubricant (Device)
结局指标
主要结局
Median Percentage of CD4 Positive T-Cells
时间窗: Baseline, Post-Intervention (Day 8)
HIV target cell availability will be assessed by the median percentage of CD4+ T cells that express HIV co-receptor CCR5 as measured prior to product use and on day 8 after product use.
Median Cumulative Amount of p24
时间窗: Baseline, Post-Intervention (Day 8)
The median cumulative amount of p24 produced in a rectal explant challenge assay as measured by ELISA from participants prior to product use and on day 8 after product use.
次要结局
- Median Rectal Tissue Tenofovir (TDF) Concentration(Post-Intervention (Day 8))
- Median Rectal Tissue Emtricitabine (FTC) Concentration(Post-Intervention (Day 8))
- Median Plasma Tenofovir (TDF) Concentration(Post-Intervention (Day 8))
- Median Rectal Secretion Emtricitabine (FTC) Concentration(Post-Intervention (Day 8))
- Median Plasma Emtricitabine (FTC) Concentration(Post-Intervention (Day 8))
- Median Peripheral Blood Mononuclear Cell (PBMC) Tenofovir (TDF) Concentration(Post-Intervention (Day 8))
- Median Rectal Secretion Tenofovir (TDF) Concentration(Post-Intervention (Day 8))
- Median Peripheral Blood Mononuclear Cell (PBMC) Emtricitabine (FTC) Concentration(Post-Intervention (Day 8))
- Median Rectal Tissue Deoxyadenosine Triphosphate (dATP) Concentration(Baseline, Post-Intervention (Day 8))
- Median Rectal Tissue Deoxycytidine Triphosphate (dCTP) Concentration(Baseline, Post-Intervention (Day 8))
- Median Peripheral Blood Mononuclear Cell (PBMC) Deoxyadenosine Triphosphate (dATP) Concentration(Baseline, Post-Intervention (Day 8))
研究者
Colleen Kelley
Assistant Professor
Emory University