Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens
Condition: HIV/AIDS
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: Genvoya
Intervention description: 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.
Intervention MeSH terms: Tenofovir; Emtricitabine; Cobicistat; Emtricitabine tenofovir alafenamide; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Elvitegravir
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: Male
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: No
Keywords: HIV; MSM; Anti-retrovirals; Pharmacokinetics; Peri-exposure HIV prophylaxis

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. HIV-negative man who reports receptive anal sex with another man in the last 6 months

          2. Aged 18-49 years

          3. Not currently taking PrEP and no plans to initiate during study

          4. Not currently taking PEP

          5. Able to provide informed consent in English

          6. No plans for relocation in the next 3 months

          7. Willing to undergo peripheral blood, penile swabs, urine, and rectal biopsy sampling

          8. Willing to use study products as directed

          9. 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.

         10. Hepatitis B surface antigen (HBsAg) must be negative (screening lab test)

         11. Creatine clearance >60 ml/min

        Exclusion Criteria:

          1. 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

          2. Currently infected with hepatitis virus and/ or have liver disease

          3. Current or chronic history of kidney disease

          4. Significant laboratory abnormalities at baseline visit, including but not limited to:

               1. Hgb ≤ 10 g/dL

               2. Partial thromboplastin time (PTT) > 1.5x upper limit of normal (ULN) or
                  international normalized ratio (INR) > 1.5x ULN

               3. Platelet count <100,000

               4. Creatinine clearance <60

               5. HBsAg reactive

          5. 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:

               1. Uncontrolled or severe cardiac arrhythmia

               2. Recent major abdominal, cardiothoracic, or neurological surgery

               3. History of uncontrolled bleeding diathesis

               4. History of colonic, rectal, or vaginal perforation, fistula, or malignancy

               5. History or evidence on clinical examination of ulcerative, suppurative, or
                  proliferative lesions of the anorectal mucosa, or untreated sexually transmitted
                  disease with mucosal involvement

          6. Continued need for, or use during the 14 days prior to enrollment, of the following
             medications:

               1. Aspirin or more than 4 doses of NSAIDs

               2. Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation
                  inhibitors, or fibrinolytic agents

               3. Any form of rectally administered agent besides lubricants or douching used for
                  sexual intercourse

          7. Continued need for, or use during the 90 days prior to enrollment, of the following
             medications:

               1. Systemic immunomodulatory agents

               2. Supraphysiologic doses of steroids (short course steroids less than 7 days
                  duration, allowable at the discretion of the investigators)

               3. Experimental medications, vaccines, or biologicals

          8. Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during
             the study, outside of the study procedures

          9. Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain,
             discharge, bleeding, etc.)

         10. Current use of hormonal therapy

         11. 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.

         12. 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