PrEP, Lube, and the Rectal Mucosa in MSM at Risk of HIV

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Defining the Rectal Mucosa in Men Who Have Sex With Men at Risk of HIV Infection

Conditions
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HIV

Intervention / Treatment
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* Drug: Truvada
* Device: Gel lubricant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rectal Gel Lubricant<br>Subjects will insert 5 mL of lubricant in rectum for seven consecutive days | Device: Gel lubricant<br>* Five ml of an over the counter sexual lubricant will be dispensed using an applicator.<br>|
| Active Comparator: Truvada<br>Subjects will take one Truvada tablet orally for seven consecutive days | Drug: Truvada<br>* Truvada is a combination of 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate taken orally.<br>* Other names: Tenofovir;|
| Active Comparator: Rectal Gel Lubricant + Truvada<br>Subjects will insert 5 mL of lubricant in rectum and take one Truvada tablet orally for seven consecutive days | Drug: Truvada<br>* Truvada is a combination of 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate taken orally.<br>* Other names: Tenofovir;Device: Gel lubricant<br>* Five ml of an over the counter sexual lubricant will be dispensed using an applicator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Percentage of CD4 Positive T-Cells | 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. | Baseline, Post-Intervention (Day 8) | 
| Median Cumulative Amount of p24 | 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. | Baseline, Post-Intervention (Day 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Plasma Emtricitabine (FTC) Concentration | Median plasma FTC concentration as measured in ng/ml prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Post-Intervention (Day 8) | 
| Median Plasma Tenofovir (TDF) Concentration | Median plasma TDF concentration as measured in ng/ml prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Post-Intervention (Day 8) | 
| Median Rectal Secretion Emtricitabine (FTC) Concentration | Median rectal secretions FTC concentrations as measured in ng/swab prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Post-Intervention (Day 8) | 
| Median Rectal Secretion Tenofovir (TDF) Concentration | Median rectal secretions TDF concentrations as measured in ng/swab prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Post-Intervention (Day 8) | 
| Median Peripheral Blood Mononuclear Cell (PBMC) Emtricitabine (FTC) Concentration | Median blood PBMC FTC concentrations as measured in fmol/million cells prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Post-Intervention (Day 8) | 
| Median Peripheral Blood Mononuclear Cell (PBMC) Tenofovir (TDF) Concentration | Median blood PBMC TDF concentrations as measured in fmol/million cells prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Post-Intervention (Day 8) | 
| Median Rectal Tissue Emtricitabine (FTC) Concentration | Median rectal tissue FTC concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Post-Intervention (Day 8) | 
| Median Rectal Tissue Tenofovir (TDF) Concentration | Median rectal tissue TDF concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Post-Intervention (Day 8) | 
| Median Rectal Tissue Deoxyadenosine Triphosphate (dATP) Concentration | Median rectal tissue dATP concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Baseline, Post-Intervention (Day 8) | 
| Median Rectal Tissue Deoxycytidine Triphosphate (dCTP) Concentration | Median rectal tissue dCTP concentrations as measured in fmol/mg tissue prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Baseline, Post-Intervention (Day 8) | 
| Median Peripheral Blood Mononuclear Cell (PBMC) Deoxyadenosine Triphosphate (dATP) Concentration | Median blood dATP concentrations as measured in fmol/million cells prior to product use and on day 8 after product use. The higher the concentration, the better the drug distribution. | Baseline, Post-Intervention (Day 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Immunodeficiency Virus, Acquired Immune Deficiency Syndrome Virus, Pre-exposure Prophylaxis