The Women TDF-FTC Benchmark Study

NCT05057858 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: STUDY00011136R01AI155086
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The study seeks to define the expected blood levels of pre-exposure prophylaxis (PrEP) medications (tenofovir) for cisgender women taking directly observed oral PrEP therapy to understand the frequency of PrEP dosing associated with HIV protection in cisgender women. Cisgender women will be randomly assigned to receive varying frequency of weekly PrEP doses and followed for up to 16 weeks. The study will also investigate how pregnancy affects the expected blood levels to help define optimal dosing of PrEP for HIV prevention during pregnancy.

Conditions

HIV Infections

Keywords

Pre-exposure Prophylaxis; HIV; Kenya

Outcome Measures

Primary Outcomes (3)

• Steady state concentrations of tenofovir-diphosphate for different dosing patterns of DOT TDF/FTC PrEP

  Measured in dried blood spots, whole blood, PBMCs

  Assessed through 8 weeks

• Steady state concentrations of tenofovir for different dosing patterns of DOT TDF/FTC PrEP

  Measured in plasma, whole blood, vaginal tissue

  Assessed through 8 weeks

• Composite outcome of adverse pregnancy outcomes among pregnant women who used DOT PrEP

  Descriptive frequency indicating presence vs. absence of any adverse pregnancy outcomes. Adverse outcomes are defined as at least one of the following: spontaneous abortion (less than 20 weeks gestation), stillbirth (greater than or equal to 20 weeks gestation), preterm delivery (less than 37 weeks), or small for gestational age (less than 10th percentile using WHO norms)

  Assessed at delivery (approximately through 40 weeks gestation)

Secondary Outcomes (3)

• Frequency of Grade 2 or higher adverse events in participants

  Assessed through 8 weeks of DOT TDF/FTC PrEP

• Frequency of infant death among infants of women in the pregnant cohort

  Assessed through 12 months after delivery

• Frequency of infant Grade 2 or higher adverse events among infants of women in the pregnant cohort

  Assessed through 12 months after delivery

Study Arms (3)

Perfect Adherence

EXPERIMENTAL

Cisgender women will receive a single tablet of co-formulated 300 mg TDF/ 200mg FTC once daily (7 doses per week).

Drug: co-formulated 300 mg TDF/ 200mg FTC

Moderate Adherence

EXPERIMENTAL

Cisgender women will receive a single tablet of co-formulated 300 mg TDF/ 200mg FTC tablet 4 times per week (Monday, Tuesday, Thursday, Friday)

Drug: co-formulated 300 mg TDF/ 200mg FTC

Poor Adherence

EXPERIMENTAL

Cisgender women will receive a single tablet of co-formulated 300 mg TDF/ 200mg FTC tablet twice per week(Monday and Tuesday)

Drug: co-formulated 300 mg TDF/ 200mg FTC

Interventions

co-formulated 300 mg TDF/ 200mg FTC DRUG

Participants will be randomized into 1 of 3 groups to receive a controlled number of doses of a single tablet co-formulated 300 mg TDF/ 200mg FTC

Also known as: Truvada

Moderate Adherence; Perfect Adherence; Poor Adherence

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 would interfere with study participation
• Lack of severe anemia
• Willing to use DOT and come to clinic frequently for DOT PrEP for at least 8 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 8 weeks.
• Resides or works in catchment area with high speed internet coverage to permit video streaming
• Specific for non-pregnant cisgender women cohort
• Not pregnant or breast feeding

You may not qualify if:

• For all cisgender women
• 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®, 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
• Specific for non-pregnant cisgender women cohort
• 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.
• Specific for pregnant cisgender women cohort
• Mother has a known history of any of the following, as determined by the site investigator or designee based on maternal report and available medical records:

Sponsors & Collaborators

• University of Washington: lead
• University of Colorado, Denver: collaborator
• Kenya Medical Research Institute: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Kenya Medical Research Institute - Partners in Health Research and Development

Thika, Kenya

Location

Related Publications (2)

• Mugwanya KK, Saina M, Mugo NR, MaWhinney S, Morrow M, Schaafsma TT, Donnell D, Glidden DV, Ngure K, Brown CE, Rechkina EA, Chohan BH, Wu L, Hill E, Koome E, Akelo N, Mbaire S, Morrison SA, Kibatha M, Njeru I, Muriithi M, Coppinger C, Bushman L, Baeten JM, Anderson PL; Women Benchmark Study Team. Adherence thresholds for emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis against HIV acquisition in cisgender women: A randomized directly observed dosing study. PLoS Med. 2025 Sep 9;22(9):e1004732. doi: 10.1371/journal.pmed.1004732. eCollection 2025 Sep.

  PMID: 40924774 DERIVED

• Wu L, Saina M, Brown C, Chege D, Donnell D, Glidden DV, Ngure K, Mugo NR, Akelo N, Schaafsma T, Anderson PL, Mugwanya KK. Establishing adherence-concentration-efficacy thresholds of TDF-FTC pre-exposure prophylaxis for HIV prevention in African women: a protocol for the Women TDF-FTC Benchmark Study. Front Reprod Health. 2024 May 27;6:1325257. doi: 10.3389/frph.2024.1325257. eCollection 2024.

  PMID: 38860025 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Racivir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Kenneth K Mugwanya, MBChB, MS, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

• Peter L Anderson, PharmD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, School of Medicine: Global Health

Study Record Dates

• First Submitted: September 16, 2021
• First Posted: September 27, 2021
• Study Start: April 25, 2022
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: August 12, 2024

Record last verified: 2024-08

Locations

KE (1)