Biomarkers for Event-driven PrEP Adherence

Phase 4

Completed

• Conditions: Human Immunodeficiency Virus
• Interventions: Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)

• Registration Number: NCT04298697
• Lead Sponsor: Emory University

Brief Summary

This study aims to recruit 20 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.

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 event-driven or on-demand PrEP (ED-PrEP). This dosing regimen has patients take two doses of PrEP 2-24 hours before sex, one dose 24 hours after sex, and another dose 48 hours after sex. This proposal 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 2 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2020-02-28
• Study First Submitted: 2020-03-04
• Study First Submitted QC: 2020-03-04
• Study First Posted: 2020-03-06
• Primary Completion: 2022-08-09
• Study Completion: 2022-08-09
• Disposition First Submitted: 2023-07-19
• Disposition First Posted: 2023-07-28
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-11
• Last Update Posted: 2024-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 48

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
• <2 sexual partners in last 6 months
• Able to provide informed consent in English
• No plans for relocation in the next 4 months
• Willing to undergo peripheral blood, urine, hair, and finger stick 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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
TDF/FTC for 13 weeks	Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)	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.
TDF/FTC for 13 weeks with weekly alternating schedule	Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)	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.
TDF/FTC for 13 weeks with weekly alternating schedule every two weeks	Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)	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.
TDF/FTC for 1 week	Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)	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.

Primary Outcome Measures

Name	Time	Method
Tenofovir-diphosphate (TFV-DP) Concentration	24 Hours After Last Dose (Week 1 for Arm A, Week 13 for Arms B, C, and D)	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.

Trial Locations

Locations (1)

Hope Clinic; 🇺🇸 Atlanta, Georgia, United States