The Women TAF-FTC Benchmark Study

Phase 2

Completed

Conditions: HIV Infections

Interventions: Drug: co-formulated 25mg TAF/ 200mg FTC

Registration Number: NCT05140954

Lead Sponsor: University of Washington

Brief Summary: The study seeks to assess the safety of and define blood and tissue benchmark concentrations of tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in cisgender women using directly observed oral pre-exposure prophylaxis (PrEP) therapy with tenofovir alafenamide-emtricitabine (TAF-FTC). Cisgender women will be randomly assigned to receive varying frequencies of weekly PrEP doses and followed for up to 18 weeks.These data will help accurate interpretation of efficacy results obtained in HIV prevention trials and programs in cisgender women.

Detailed Description: This is an open-label, randomized, three-arm, directly observed therapy (DOT), pharmacokinetics study. HIV-uninfected non-pregnant cisgender women at low risk for HIV acquisition will be randomly assigned to 1 of 3 dosing frequencies of DOT with tenofovir alafenamide-emtricitabine (TAF-FTC) oral PrEP, to help differentiate poor and moderate from perfect adherence. The primary objectives of the study are:

1. To describe the safety of TAF-FTC-based PrEP in HIV-uninfected cisgender women.

2. To define expected blood concentrations and dose-proportionality specific to cisgender women for tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) and peripheral blood mononuclear cells (PBMCs) using directly observed therapy of TAF-FTC at 2, 4, and 7 doses per week, representing poor, moderate, and perfect adherence, respectively.

3. To establish a model to predict adherence rate to TAF-FTC by level of TFV-DP in DBS for cisgender women. HIV-uninfected non-pregnant cisgender women will be randomly assigned to 1 of 3 dosing frequencies of directly observed therapy of TAF-FTC oral PrEP: 2, 4, or 7 doses/week to differentiate poor and moderate from perfect adherence.

The study will be the first to define TAF-FTC-based PrEP adherence-blood concentration thresholds for African cisgender women, a priority population for HIV prevention. The findings will guide accurate interpretation of safety, adherence, and efficacy of planned or ongoing HIV prevention trials in African women.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 54

Inclusion Criteria

Age ≥18 and ≤30 years old
Willing to undergo urine pregnancy tests
Has understood the information provided and has provided written informed consent before any study-related procedures are performed.
HIV uninfected based on negative HIV rapid tests, according to Kenyan national algorithm
Normal renal function (estimated glomerular filtration rate >60 mL/min)
Hepatitis B surface Ag negative
No active clinically significant medical or psychiatric conditions that, in the opinion of the investigators, would interfere with study participation
Lack of severe anemia (Hemoglobin >10 g/dL)
Willing to use DOT and come to clinic frequently for DOT PrEP for at least 10 weeks
Willing to have home visits for follow up
Has access to an active smartphone to allow off-site observation of dosing if unable to come to the clinic or as determined by the study staff, the participant resides in close location to clinic to permit home visit if unable to come to the clinic. i.e., potential participants without a smartphone may be enrolled in the study if investigator determines that the participant resides within reasonable distance from the clinic that would permit home visit id the participant misses their visit.
Intention to stay within the study site's catchment area for at least 10 weeks.
Resides or works in catchment area with high speed internet coverage to permit video streaming
Not pregnant or breast feeding
Willing to use effective contraception during the study period.
At low risk for HIV. In Kenya, national guidelines define substantial risk for HIV and recommend PrEP be an option for individuals reporting: partner of HIV-infected person not on ART or on ART for <6 months, >1 partner of unknown status, transactional sex, recent STI, recurrent PEP use, inconsistent condom use, or injection drug use. So, non-pregnant cisgender women reporting any of these factors will not be eligible for the study but will be linked for PrEP at clinic of choice including at Thika Site itself.
Willing to be randomized to non-daily PrEP and come to clinic frequently for DOT PrEP
Willingness and ability to be abstinent for at least 7 days after each vaginal biopsy visit.

Exclusion Criteria

Inability to give informed consent
Positive screening HIV+ as determined by standard rapid serologic assays or suspected acute HIV infection in the opinion of the clinician. (example signs and symptoms of acute HIV infection include combinations of fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, and adenopathy cervical or inguinal)
Positive HBV surface antigen test at screening
Calculated creatinine clearance <60 ml/min.
Any laboratory value or uncontrolled medical conditions that, in the opinion of the investigators, would interfere with the study conditions such as, heart disease and/or cancer.
Prohibited concomitant medications are: investigational agents (within 30 days of enrollment), aminoglycosides, ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir (>800mg acyclovir or >500mg valacyclovir for >7 days), cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications including TAF®, TRUVADA®, ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of FTC and tenofovir, respectively.
Current or past use of PrEP (pre-exposure prophylaxis)
Not willing to have home visits
Pregnancy or plan to become pregnant in the next 6 months or unwillingness to use birth control
Current breastfeeding
High risk of HIV infection (for example: sexually active with an HIV infected partner; engages in condomless intercourse with HIV-infected partners or partner of unknown status during the study; females who exchange sex for money, shelter, or gifts; active injection drug use or during the last 12 months; newly diagnosed sexually transmitted infections in last 6 months.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Perfect Adherence	co-formulated 25mg TAF/ 200mg FTC	Cisgender women will receive a single tablet of coformulated 25 mg TAF/ 200mg FTC once daily (7 doses per week).
Moderate Adherence	co-formulated 25mg TAF/ 200mg FTC	Cisgender women will receive a single tablet of coformulated 25 mg TAF/ 200mg FTC 4 times per week
Poor Adherence	co-formulated 25mg TAF/ 200mg FTC	Cisgender women will receive a single tablet of coformulated 25 mg TAF/ 200mg FTC twice per week

Primary Outcome Measures

Name	Time	Method
Frequency of Adverse Events	Assessed through the 10 week DOT dosing period	The frequency of graded adverse events by arm, including emergent HIV infection during the study period.
Concentrations of Tenofovir Disphosphate (TFV-DP) and Emtricitabine Triphosphate (FTC-TP) Measured at Ten Weeks in Dried Blood Spots (DBS)	Assessed at week 10	TFV-DP and FTC-TP concentrations observed in dried blood spots (DBS) after ten weeks of directly observed therapy with TAF-FTC oral PrEP, in women randomized to receive 2, 4, or 7 doses per week, representing poor, moderate, or perfect adherence, respectively.
Concentrations of Tenofovir Disphosphate (TFV-DP) and Emtricitabine Triphosphate (FTC-TP) Measured at Four Weeks in Peripheral Blood Mononuclear Cells (PBMCs)	Assessed at week 4	Steady-state TFV-DP and FTC-TP concentrations observed in peripheral blood mononuclear cells (PBMCs) after ten weeks of directly observed therapy with TAF-FTC oral PrEP, in women randomized to receive 2, 4, or 7 doses per week, representing poor, moderate, or perfect adherence, respectively.
Fitted Steady-state TFV-DP Concentrations in Dried Blood Spots (DBS)	Assessed through 10 weeks	Fitted steady-state TFV-DP concentrations after ten weeks of directly observed therapy with TAF-FTC oral PrEP, in women randomized to receive 2, 4, or 7 doses per week, representing poor, moderate, or perfect adherence, respectively.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (1): Kenya Medical Research Institute - Partners in Health Research and Development
🇰🇪
Thika, Kenya
Kenya Medical Research Institute - Partners in Health Research and Development
🇰🇪Thika, Kenya