Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens

Study Overview
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Brief Summary
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This study is being conducted to determine if the uptake of anti-HIV medication, called Genvoya®, at different time-frames, is different at several body sites, including mucosal tissues. This medication might be considered for on-demand PEP regimens in the future.

Detailed Description
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Men who have sex with men (MSM) continue to be disproportionately affected by HIV. The majority of MSM acquire HIV after exposure to the rectal mucosa through unprotected receptive anal intercourse. Post-exposure-prophylaxis (PEP) is an intervention that is used to prevent HIV infection soon (72 hours) after a potential exposure. HIV-negative people with a possible exposure to HIV are instructed to take 28 days of a combination anti-HIV medication regimen, Truvada® + Raltegravir. This study is being conducted to determine if the uptake of another anti-HIV medication, called Genvoya®, at different time-frames, is different at several body sites, including mucosal tissues. This medication might be considered for on-demand PEP regimens in the future.

Official Title
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Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens

Conditions
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HIV/AIDS

Intervention / Treatment
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* Drug: Genvoya


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 Not currently taking PrEP and no plans to initiate during study Not currently taking PEP Able to provide informed consent in English No plans for relocation in the next 3 months Willing to undergo peripheral blood, penile swabs, urine, and rectal biopsy sampling Willing to use study products as directed Willing to abstain from receptive anal intercourse 3 days prior to starting study product and for the duration of the study and for 7 days after any rectal biopsy procedure. Hepatitis B surface antigen (HBsAg) must be negative (screening lab test) Creatine clearance >60 ml/min 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 Currently infected with hepatitis virus and/ or have liver disease Current or chronic history of kidney disease Significant laboratory abnormalities at baseline visit, including but not limited to: Hgb ≤ 10 g/dL Partial thromboplastin time (PTT) > 1.5x upper limit of normal (ULN) or international normalized ratio (INR) > 1.5x ULN Platelet count <100,000 Creatinine clearance <60 HBsAg reactive 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 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 NSAIDs Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents Any form of rectally administered agent besides 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 (short course steroids less than 7 days duration, allowable at the discretion of the investigators) 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 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. Participants taking potent inhibitors (e.g. itraconazole, diltiazem) or inducers (e.g. rifampin, phenytoin) of the CYP3A4 enzyme that also metabolizes Genvoya will be excluded from the study

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Pre-drug<br>Participants enrolled in the pre-drug arm will not receive any drug. At visit 2, they will undergo blood, urine, penile swab, cheek swab, rectal swab and rectal biopsy collection. | |
| Experimental: Genvoya - 2 and 48 hours specimen collection<br>Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5). | Drug: Genvoya<br>* Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.<br>* Other names: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide;|
| Experimental: Genvoya - 4 and 72 hours specimen collection<br>Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5). | Drug: Genvoya<br>* Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.<br>* Other names: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide;|
| Experimental: Genvoya - 24 and 96 hours specimen collection<br>Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5). | Drug: Genvoya<br>* Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.<br>* Other names: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide;|
| Experimental: Genvoya - Single time point specimen collection<br>Specimen collection 8 hours after taking the medication in the clinic (visit 4). | Drug: Genvoya<br>* Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat. At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.<br>* Other names: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of Tenofovir (TFV) | Median drug concentrations of the TFV component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. | Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication | 
| Plasma Concentration of Emtricitabine (FTC) | Median drug concentrations of the FTC component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. | Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication | 
| Plasma Concentration of Elvitegravir (EVG) | Median drug concentrations of the EVG component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. | Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral Blood Mononuclear Cell (PBMC) Concentration of Tenofovir-diphosphate (TFV-DP) | A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus: lymphocytes (T cells, B cells, natural killer (NK) cells) and monocytes. Median drug concentrations were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. | Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication | 
| Peripheral Blood Mononuclear Cell (PBMC) Concentration of Emtricitabine-triphosphate (FTC-TP) | A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus: lymphocytes (T cells, B cells, NK cells) and monocytes. Median drug levels were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. | Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, MSM, Anti-retrovirals, Pharmacokinetics, Peri-exposure HIV prophylaxis