Antiretroviral Therapy (ART) Persistence in Different Body Compartments in HIV Negative MSM

NCT ID: NCT04039217

Last Updated: 2022-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-30
• Study Completion Date: 2020-08-28

Brief Summary

The study seeks to understand how anti-HIV drug Biktarvy, which contains the drugs tenofovir alafenamide (TAF), emtricitabine (FTC), and bictegravir (BIC) is absorbed and how long it persists in different body compartments, including mucosal tissues, as it may be considered for PrEP or 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 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 considered for future development. The study drug provided in this study will not protect participants from HIV or treat any active infection. This proposal seeks to understand how other anti-HIV medications are absorbed and how long they persist in different body compartments, including mucosal tissues, as they may be considered for PrEP or PEP regimens in the future.

Participants will be sequentially enrolled into study arms. All participants will take two doses of Biktarvy and then will have biological samples collected at different time points. Blood will be collected at three different time points and a rectal biopsy will occur once. Participants may participate in more than one study arm or subgroup; however, at least 6 weeks must lapse after completion of one study arm or subgroup, before entry into another.

Median drug levels of TAF, FTC, and BIC in plasma, peripheral blood mononuclear cells (PBMCs) and rectal tissues will be calculated at baseline, 24 hours after the first dose and 120 hours after the first dose as the primary outcomes of this study. Samples collected at other time points will be stored for future exploratory analyses.

Conditions

ART; HIV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Sample collection 2, 48, and 96 hours after first dose of Biktarvy

Participants in this study arm (Arm A) will provide biological specimens 2, 48, and 96 hours after the in-clinic dose of Biktarvy. Approximately 24 mL of blood will be drawn, an oral cheek swab, 1 pre-wet penile swab and 1 dry penile swab, and a urethral swab will be collected. After previous swab collections are complete, participants will be asked to provide a urine sample (some of which will be used for gonorrhea and chlamydia testing). Participants will undergo rectal biopsy collection at one of the study visits.

Group Type: EXPERIMENTAL

Biktarvy

Intervention Type: DRUG

Participants will be given two doses of the oral fixed dose combination anti-HIV medication Biktarvy (BIC/FTC/TAF) separated by 24 hours. The first dose is given in the clinic and participants are instructed to take the second dose at home, 24 hours after the first dose.

Sample collection 4, 26, and 120 hours after first dose of Biktarvy

Participants in this study arm (Arm B) will provide biological specimens 4, 26, and 120 hours after the in-clinic dose of Biktarvy. Approximately 24 mL of blood will be drawn, an oral cheek swab, 1 pre-wet penile swab and 1 dry penile swab, and a urethral swab will be collected. After previous swab collections are complete, participants will be asked to provide a urine sample (some of which will be used for gonorrhea and chlamydia testing). Participants will undergo rectal biopsy collection at one of the study visits.

Group Type: EXPERIMENTAL

Biktarvy

Intervention Type: DRUG

Participants will be given two doses of the oral fixed dose combination anti-HIV medication Biktarvy (BIC/FTC/TAF) separated by 24 hours. The first dose is given in the clinic and participants are instructed to take the second dose at home, 24 hours after the first dose.

Sample collection 24, 28, and 72 hours after first dose of Biktarvy

Participants in this study arm (Arm C) will provide biological specimens 24, 28, and 72 hours after the in-clinic dose of Biktarvy. Approximately 24 mL of blood will be drawn, an oral cheek swab, 1 pre-wet penile swab and 1 dry penile swab, and a urethral swab will be collected. After previous swab collections are complete, participants will be asked to provide a urine sample (some of which will be used for gonorrhea and chlamydia testing). Participants will undergo rectal biopsy collection at one of the study visits.

Group Type: EXPERIMENTAL

Biktarvy

Intervention Type: DRUG

Participants will be given two doses of the oral fixed dose combination anti-HIV medication Biktarvy (BIC/FTC/TAF) separated by 24 hours. The first dose is given in the clinic and participants are instructed to take the second dose at home, 24 hours after the first dose.

Interventions

Biktarvy

Participants will be given two doses of the oral fixed dose combination anti-HIV medication Biktarvy (BIC/FTC/TAF) separated by 24 hours. The first dose is given in the clinic and participants are instructed to take the second dose at home, 24 hours after the first dose.

Intervention Type: DRUG

Other Intervention Names

BIC/FTC/TAF

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, 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 will be excluded from the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Colleen Kelley

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Colleen Kelley, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Hope Clinic

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00111410

Identifier Type: -

Identifier Source: org_study_id