Biomarkers for Event-driven PrEP Adherence

Study Overview
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Brief Summary
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This study aims to recruit 20 participants who will take the combination anti-HIV drug tenofovir+emtricitabine (TDF/FTC) at specified times. Participants will then provide biologic samples for the measurement of anti-retroviral drug concentrations in various body compartment sites. Participants will be involved in the study for up to 24 weeks.

Detailed Description
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Men who have sex with men (MSM) continue to be disproportionately affected by HIV. In 2014, MSM made up approximately 2% of the U.S. population but accounted for 70% of the new HIV infections. The majority of MSM acquire HIV after exposure to the rectal mucosa through receptive anal intercourse without condoms. Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are recommended for MSM who may be exposed to HIV to prevent infection. Current recommendations for PrEP are to take the combination anti-HIV drug, tenofovir+emtricitabine (TDF/FTC), on a daily basis for the duration of someone's HIV risk exposure period, which could be months or years. For PEP, a three-drug anti-HIV medication is recommended within 72 hours of a possible exposure for a 28-day course. While PrEP and PEP are effective, some people find it difficult to follow the recommended regimen. Therefore, additional short-course dosing regimens for PrEP and PEP are being implemented, such as event-driven or on-demand PrEP (ED-PrEP). This dosing regimen has patients take two doses of PrEP 2-24 hours before sex, one dose 24 hours after sex, and another dose 48 hours after sex. This proposal seeks to evaluate the usefulness of biomarkers to confirm self-reported adherence to ED-PrEP in MSM. The study drug provided in this study will not protect participants from HIV or treat any active infection. This study will recruit 40 HIV-negative MSM aged 18-59 in good general health. Participants will be sequentially assigned to one of 2 study arms which will determine when they will take doses of the study drug and give specimen samples. All participants will provide written informed consent at the first study visit and undergo a screening medical history, physical exam, and safety laboratory tests. All participants will take at least 4 doses (pills) of the study drug. At study visits, participants will return to donate blood, hair, and urine samples, and a finger stick. All biologic specimens collected will be transferred to the Centers for Disease Control and Prevention (CDC) on the day of collection for measurement of drug levels.

Official Title
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Biomarkers for Event-driven PrEP Adherence

Conditions
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Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: TDF/FTC Dose Schedule for Arm A
* Drug: TDF/FTC Dose Schedule for Arm B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-negative person, who was assigned male at birth, who reports sex with another man in the last year, and is in good general health. Not currently taking PrEP and no plans to initiate during study Not currently taking PEP Consistent condom use and willing to use condoms for the duration of the study <2 sexual partners in last 6 months Able to provide informed consent in English No plans for relocation in the next 4 months Willing to undergo peripheral blood, urine, hair, and finger stick sampling. Willing to use study products as directed Hepatitis B surface antigen (HBsAg) must be negative (screening lab test) Creatinine clearance (CrCl) >60 ml/min Exclusion Criteria: Currently infected with hepatitis virus and/ or has liver disease Current or chronic history of kidney disease or CrCl<60 ml/min Continued need for, or use during the 90 days prior to enrollment, of the following medications: Systemic immunomodulatory agents Supraphysiologic doses of steroids (short course steroids less than 7 days duration, allowable at the discretion of the investigators) Chemotherapy or radiation for treatment of malignancy Experimental medications, vaccines, or biologicals Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during the study, outside of the study procedures 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: 59 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TDF/FTC for one week<br>The first 10 participants (Arm A) will take TDF/FTC for three consecutive days of one week and will have biologic specimens collected at 8 study time points. | Drug: TDF/FTC Dose Schedule for Arm A<br>* TDF/FTC is a combination anti-HIV medication that contains the drugs tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Participants will take 2 pills on Study Day 1, then one pill per day on Study Days 2 and 3. Participants will have biologic specimens collected at specific time points until 28 days after the last dose.<br>* Other names: Truvada;|
| Experimental: TDF/FTC for four weeks<br>The second 10 participants (Arm B) will take TDF/FTC for three consecutive days for four weeks and will have biologic specimens collected at 20 study time points. | Drug: TDF/FTC Dose Schedule for Arm B<br>* TDF/FTC is a combination anti-HIV medication that contains the drugs tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Participants will be on a weekly dosing schedule of 2 pills on the first day, followed by one pill per day for the next two days. They will follow this dosing schedule for four weeks. Participants will have biologic specimens collected at specific time points until 28 days after the last dose.<br>* Other names: Truvada;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tenofovir-diphosphate (TFV-DP) Concentration | Median TFV-DP concentrations in dried blood spots will be measured 24 hours after the last dose in both study arms to compare accumulation of drug following weekly ED-PrEP dosing. | 24 Hours After Last Dose (Day 4 for Arm A, Day 29 for Arm B) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pre-exposure prophylaxis (PrEP), Post-exposure prophylaxis (PEP)