Novel Approaches for Quantitative Assessment of Adherence

Approximately twelve healthy adult volunteers with no contraindicated medical conditions or medications will be recruited from CU/Denver and the surrounding community.

Participants will be randomized to one of 2 sequences consisting of two directly observed dosing regimens with 2mg adenine 5+ per dose, 1 dose/week followed by 4 doses/week or 3 doses/week followed by 7 doses/week. Each dose regimen will have a duration of approximately 12 weeks and will be separated by an approximately 12-week washout period for a total study duration of approximately 36 weeks. The rationale for this study design is several fold. First, the lower doses are given initially to minimize the potential effects of carry-over in the second regimen. Second, 1 to 7 doses/week encompass a wide range of simulated adherence rates to assess the promise of this taggant, adenine 5+, as an adherence biomarker. Third, the 12 week duration is designed to achieve ~90% of steady-state given an estimated half-life of 20-30 days.

Inclusion:

• Ambulatory 18-40 year old adults.
• Ability to comply with study procedures, including directly observed dosing visits and availability and use of video streaming technology.

Exclusion:

• Inability to give informed consent
• Pregnancy or plan to become pregnant in the next 12 months or unwillingness to use birth control
• Current breastfeeding
• Active psychiatric illness, social condition, or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements.
• GFR estimate < 60 ml/min (MDRD equation).
• Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal
• Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL.
• Symptomatic hemoglobinopathies or active hemolysis.
• 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.
• Any investigational agents within 30 days of enrollment.
• Plan to donate blood or plasma during study enrollment.