Clinical trial NCT03976752: Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens
Official title: Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV/AIDS
Keywords: HIV
MSM
Anti-retrovirals
Pharmacokinetics
Peri-exposure HIV prophylaxis
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2019-06-06
Enrollment: 41
Sex: MALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Plasma Concentration of Tenofovir (TFV)
timeFrame: Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication
measure: Plasma Concentration of Emtricitabine (FTC)
timeFrame: Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication
measure: Plasma Concentration of Elvitegravir (EVG)
timeFrame: Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication
Secondary outcomes:
measure: Peripheral Blood Mononuclear Cell (PBMC) Concentration of Tenofovir-diphosphate (TFV-DP)
timeFrame: Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication
measure: Peripheral Blood Mononuclear Cell (PBMC) Concentration of Emtricitabine-triphosphate (FTC-TP)
timeFrame: Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication
Other outcomes:
measure: Rectal Tissue Concentration of Tenofovir (TFN)
timeFrame: Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication
measure: Rectal Tissue Concentration of Emtricitabine (FTC)
timeFrame: Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication
measure: Rectal Tissue Concentration of Elvitegravir (EVG)
timeFrame: Baseline, and 2, 4, 8, 24, 72, 96 hours after taking the second dose of medication
measure: Rectal Tissue Concentration of Tenofovir-diphosphate (TFV-DP)
timeFrame: Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication
measure: Rectal Tissue Concentration of Emtricitabine-triphosphate (FTC-TP)
timeFrame: Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication
Locations:
city: Atlanta
country: United States
facility: Hope Clinic
state: Georgia
Study officials:
affiliation: Emory University
name: Colleen Kelley, MD
role: PRINCIPAL_INVESTIGATOR
References: