Biomarkers for Event-driven PrEP Adherence

This study aims to recruit 40 participants who will take the combination anti-HIV drug tenofovir+emtricitabine (TDF/FTC) at specified times. Participants will then provide biologic samples for the measurement of anti-retroviral drug concentrations in various body compartment sites. Participants will be involved in the study for up to 24 weeks.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus
• Intervention / Treatment: Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)

Detailed Description

Men who have sex with men (MSM) continue to be disproportionately affected by HIV. In 2014, MSM made up approximately 2% of the U.S. population but accounted for 70% of the new HIV infections. 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 implemented, such as on-demand or event-driven PrEP (ED-PrEP). This dosing regimen has patients take two doses of PrEP 2 to 24 hours before sex, one dose 24 hours after sex, and another dose 48 hours after sex. This study seeks to evaluate the usefulness of biomarkers to confirm self-reported adherence to ED-PrEP in MSM. The study drug provided in this study will not protect participants from HIV or treat any active infection.

This study will recruit 40 HIV-negative MSM aged 18-59 in good general health. Participants will be sequentially assigned to one of four study arms which will determine when they will take doses of the study drug and give specimen samples. All participants will provide written informed consent at the first study visit and undergo a screening medical history, physical exam, and safety laboratory tests. All participants will take at least 4 doses (pills) of the study drug. At study visits, participants will return to donate blood, hair, and urine samples, and a finger stick. All biologic specimens collected will be transferred to the Centers for Disease Control and Prevention (CDC) on the day of collection for measurement of drug levels.

• Study Type: Interventional
• Enrollment (Actual): 43
• 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 59 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• HIV-negative person, who was assigned male at birth, who reports sex with another man in the last year, and is in good general health.
• Not currently taking PrEP and no plans to initiate during study
• Not currently taking PEP
• Consistent condom use and willing to use condoms for the duration of the study
• Able to provide informed consent in English
• No plans for relocation in the next 4 months
• Willing to undergo peripheral blood, urine, hair, finger stick, and optional hair sampling
• Willing to use study products as directed
• Hepatitis B surface antigen (HBsAg) must be negative (screening lab test)
• Creatinine clearance (CrCl) >60 ml/min

Exclusion Criteria:

• Currently infected with hepatitis virus and/ or has liver disease
• Current or chronic history of kidney disease or CrCl<60 ml/min

• Continued need for, or use during the 90 days prior to enrollment, of the following medications:

  • Systemic immunomodulatory agents
  • Supraphysiologic doses of steroids (short course steroids less than 7 days duration, allowable at the discretion of the investigators)
  • Chemotherapy or radiation for treatment of malignancy
  • Experimental medications, vaccines, or biologicals
• Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during the study, outside of the study procedures
• Current use of hormonal therapy
• 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

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TDF/FTC for 1 week; The first 10 participants (Arm A) will take TDF/FTC for three consecutive days of one week, taking 2 pills on the first day and one pill on the second and third day, for a total of 4 doses.	Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC); TDF/FTC is a combination anti-HIV medication that contains the drugs tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Participants will take 2 pills on the first day of the week and one pill per day on the second and third days of the week, according to the dosing schedule of the study arm they are in. Participants will have biologic specimens collected at specific time points until 28 days after the last dose.; Other Names: Truvada
Experimental: TDF/FTC for 13 weeks; The second 10 participants (Arm B) will take TDF/FTC for three consecutive days for thirteen weeks, taking 2 pills on the first day and one pill on the second and third day of each week, for a total of 52 doses.	Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC); TDF/FTC is a combination anti-HIV medication that contains the drugs tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Participants will take 2 pills on the first day of the week and one pill per day on the second and third days of the week, according to the dosing schedule of the study arm they are in. Participants will have biologic specimens collected at specific time points until 28 days after the last dose.; Other Names: Truvada
Experimental: TDF/FTC for 13 weeks with weekly alternating schedule; The third 10 participants (Arm C) will take TDF/FTC for three consecutive days, alternating weeks over a 13-week period, taking 2 pills on the first day and one pill on the second and third day of each dosing week, for a total of 28 doses.	Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC); TDF/FTC is a combination anti-HIV medication that contains the drugs tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Participants will take 2 pills on the first day of the week and one pill per day on the second and third days of the week, according to the dosing schedule of the study arm they are in. Participants will have biologic specimens collected at specific time points until 28 days after the last dose.; Other Names: Truvada
Experimental: TDF/FTC for 13 weeks with weekly alternating schedule every two weeks; The fourth 10 participants (Arm D) will take TDF/FTC for three consecutive days over a 13-week period, alternating two weeks of study medication followed by two weeks with no medication, taking 2 pills on the first day and one pill on the second and third day of dosing each week, for a total of 28 doses.	Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC); TDF/FTC is a combination anti-HIV medication that contains the drugs tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Participants will take 2 pills on the first day of the week and one pill per day on the second and third days of the week, according to the dosing schedule of the study arm they are in. Participants will have biologic specimens collected at specific time points until 28 days after the last dose.; Other Names: Truvada

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tenofovir-diphosphate (TFV-DP) Concentration	Concentration of TFV-DP was measured 24 hours after the last dose to compare accumulation of drug following weekly event-driven PrEP (ED-PrEP) dosing. Dried blood spot samples were collected from participants using a 6 millimeter (mm) dried blood spot card punch system.	24 Hours After Last Dose (Week 1 for Arm A, Week 13 for Arms B, C, and D)

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Colleen Kelley, MD, MPH, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2020
• Primary Completion (Actual): August 9, 2022
• Study Completion (Actual): August 9, 2022

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 6, 2020

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: August 27, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Pre-exposure prophylaxis (PrEP); Post-exposure prophylaxis (PEP)
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine
• Other Study ID Numbers: IRB00116781; CDC-IRB00116781 (Other Identifier: Centers for Disease Control and Prevention)

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 made available for sharing.
• IPD Sharing Time Frame: Data will become available to researchers who provide a methodologically sound proposal, beginning 9 months and ending at 36 months following publication.
• 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