Project ADHERE: Clinical Proof-of-Concept of a Tenofovir (TFV) Aptamer-Based Biosensor
Condition: HIV/AIDS; Adherence, Medication; Drug Use
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Truvada®, an oral pill comprised of two anti-retroviral compounds, emtricitabine (FTC) and
      tenofovir disoproxil fumarate (TDF), is currently the only drug combination approved for
      pre-exposure prophylaxis (PrEP) in women exposed to high HIV risk through vaginal
      acquisition. Adherence to the one pill per day regimen is crucial for its effectiveness in
      reducing the risk of acquiring HIV. Currently, there is no available point of care diagnostic
      test to quickly measure blood levels of tenofovir in the clinic. This study will determine
      whether a tenofovir (TFV) aptamer-based biosensor (aptasensor) can detect TFV in biological
      fluids from women randomized to different dosing regimens representing high and low
      adherence.
    

Detailed description: 
      Project ADHERE is a pilot, prospective, randomized study which will screen approximately 20
      healthy, non-pregnant, HIV negative, premenopausal women (aged 18-50) at Eastern Virginia
      Medical School (EVMS) who are not at risk of pregnancy and are at low risk for sexually
      transmitted infections (STIs) in order to have approximately 14 women complete all study
      visits. The women will be randomized to one of two different dosing regimens of Truvada for
      up to 14 days. The low adherence cohort will take a total of 3 Truvada pills per week while
      the high adherence cohort will be assigned to take daily dosing, 7 pills per week. At
      screening (visit 1), we will screen women for HIV-1 and perform STI tests and serum screening
      for Hepatitis B and creatinine clearance prior to commencing oral PrEP, consistent with oral
      PrEP initiation guidelines. After screening labs return, they will come to the clinic for
      visit 2 when baseline blood, urine, and vaginal fluid will be collected, randomize
      participants to the dosing regimen, watch the participants ingest the first dose, and then
      direct to them to take subsequent doses in their homes. Reminder text messages will be sent
      to the participants to facilitate doses being taken at the same time of day upon which they
      will text message the coordinator after ingesting the pill. Participants will return 24
      hours, 7 days, and 14 days after visit 2 for pre-dose collection of blood, urine, and vaginal
      fluid samples (visits 3, 4, and 5, respectively). For all visits, participants will not to
      take the next prescribed dose before coming to the clinic. Once samples are collected,
      participants will ingest the next scheduled pill. However, for the high adherence regimen,
      the women will take their last dose on day 14 and then come to the clinic 24 hours later on
      day 15 for collection of samples. Regardless of regimen, sample collection will take place no
      earlier than 24 hours after last dosing to prevent white coat effects. Samples will be
      brought to the laboratory for processing and eventual measurement of TFV levels by the TFV
      aptasensor. Aliquots of plasma and urine will also be analyzed by Liquid
      Chromatography-Tandem Mass Spectrometry (LC-MS/MS) so sensitivity and specificity of the
      aptasensor can be determined. The ability of the TFV aptasensor to distinguish levels
      associated with high and low adherence will also be assessed.
    

Intervention name(s): Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC)
Intervention type(s): Drug
Intervention description(s): Women will take 1 pill orally according the dosing regimen of the arm to which they are assigned
Other intervention name(s): Truvada
Intervention MeSH terms: Tenofovir; Emtricitabine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Women will be randomized into one of two groups: high adherence (7 pills/week) and how adherence (3 pills/week)
Masking: Single (Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: HIV PrEP; biosensor; tenofovir