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

NCT04039217 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IRB00111410
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

ART; HIV

Keywords

PrEP; PEP; MSM; Short-course regimen; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (3)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Interventions

Biktarvy 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.

Also known as: BIC/FTC/TAF

Sample collection 2, 48, and 96 hours after first dose of Biktarvy; Sample collection 24, 28, and 72 hours after first dose of Biktarvy; Sample collection 4, 26, and 120 hours after first dose of Biktarvy

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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, 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Hope Clinic

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination

Results Point of Contact

• Title: Dr. Colleen Kelley
• Organization: Emory University

colleen.kelley@emory.edu

404-712-1823

Study Officials

• Colleen Kelley, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: July 31, 2019
• Study Start: September 30, 2019
• Primary Completion: August 28, 2020
• Study Completion: August 28, 2020
• Last Updated: February 22, 2022
• Results First Posted: February 22, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will become available Beginning 9 months and ending at 36 months following publication to researchers who provide a methodologically sound proposal.
• Access Criteria: Proposals should be directed to colleen.kelley@emory.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)