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

ART Persistence: Antiretroviral Drug Persistence in Different Body Compartments in HIV Negative Men Who Have Sex With Men

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.

Study Overview

• Status: Completed
• Conditions: HIV; ART
• Intervention / Treatment: Drug: Biktarvy

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Hope Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.; Other Names: BIC/FTC/TAF
Experimental: 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.	Drug: 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.; Other Names: BIC/FTC/TAF
Experimental: 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.	Drug: 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.; Other Names: BIC/FTC/TAF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Drug Levels in Plasma	Median drug levels of tenofovir (TFV), emtricitabine (FTC), and bictegravir (BIC) in plasma were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are plasma concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.	Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose
Median Drug Concentration in Peripheral Blood Mononuclear Cells (PBMCs)	Median drug concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in PBMCs were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are PBMC concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.	Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose
Median Drug Levels in Rectal Tissues	Median drug levels of TFV, FTC, and BIC in rectal tissue were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are rectal tissue concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.	Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Colleen Kelley, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): August 28, 2020
• Study Completion (Actual): August 28, 2020

Study Registration Dates

• First Submitted: July 29, 2019
• First Submitted That Met QC Criteria: July 29, 2019
• First Posted (Actual): July 31, 2019

Study Record Updates

• Last Update Posted (Actual): February 22, 2022
• Last Update Submitted That Met QC Criteria: January 28, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Pharmacokinetics; PrEP; MSM; PEP; Short-course regimen
• Other Study ID Numbers: IRB00111410

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after de-identification (e.g., text, tables, figures, and appendices), will be available for sharing.
• IPD Sharing Time Frame: Data will become available Beginning 9 months and ending at 36 months following publication to researchers who provide a methodologically sound proposal.
• IPD Sharing Access Criteria: Proposals should be directed to colleen.kelley@emory.edu. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No