PrEP Adherence Monitoring
Conditions
Keywords
Pre exposure prophylaxis, Dried blood spots
Brief summary
The primary objective of this study is to define the mean, variance, and dose proportionality for tenofovir-diphosphate(TFV-DP) in dried blood spots resulting from 33%, 67%, and 100% of daily dosing with 200mg emtricitabine and 300mg of tenofovir disoproxil fumarate (as Truvada®). With this information, a model will be established to predict adherence rates to TFV-DP using DBS. Forty-eight healthy HIV-uninfected adult participants who are at low risk for HIV infection will be randomized to one of 6 sequences consisting of two directly observed dosing regimens, 33%/67%, 33%/100%, 67%/33%, 67%/100%, 100%/33%, and 100%/67% with each dose regimen lasting approximately 12 weeks, separated by an approximately 12 week washout period. DBS will be collected at regular intervals, including during the washout. The hypothesis of the study is that levels of TFV-DP in DBS will predict adherence rates in the preceding 1-3 months.
Interventions
DRUGTruvada
Truvada is a combination pill consisting of tenofovir and emtricitabine used in PrEP
Sponsors
San Francisco Department of Public Health
National Institute of Allergy and Infectious Diseases (NIAID)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Ambulatory 18-50 year old adults. Enrollment will target approximately half women and approximately one third African-Americans and one third Latino. 2. Ability to comply with study procedures, including directly observed dosing visits and availability and use of audio-video streaming technology.
Exclusion criteria
1. Inability to give informed consent 2. A minimum scalp hair length of 2 cm in the occipital region. 3. Pregnancy or plan to become pregnant or unwillingness to use birth control 4. Current breastfeeding. 5. High risk of HIV-1 infection (for example: sexually active with an HIV infected partner; men who have sex with men who may engage in condom-less intercourse with HIV-infected partners or partner of unknown status during the study; males or 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) 6. Positive screening HIV+ ELISA 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) 7. Positive Hepatitis B (HBV) surface antigen test at screening 8. Active psychiatric illness, social condition, or alcohol/drug abuse that, in the opinion of the investigators, would interfere with study requirements. 9. History of non-traumatic, pathologic bone fractures 10. Glomerular Filtration Rate (GFR, creatinine clearance) \< 60 ml/min (MDRD equation). 11. Urine dipstick protein ≥ 2+ 12. Total bilirubin and/or hepatic transaminases (ALT and AST) ≥ 2.5x upper limit of normal 13. Absolute neutrophil count ≤ 1,500/mm3, platelets count ≤ 100,000/mm3, or hemoglobin ≤ 10 g/dL. 14. Medical condition that alters red blood cell kinetics including hemoglobinopathies or active hemolysis. 15. Any laboratory value or uncontrolled medical conditions that would interfere with the study conditions such as, heart disease and/or cancer. 16. Contraindicated concomitant medications (including investigational agents, aminoglycosides, ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir, cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications (Truvada®) including ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of Emtricitabine (FTC) and tenofovir, respectively).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steady State Concentrations of TFV-DP for Different Dosing Patterns of Truvada | Assessed every 2 weeks during the dosing periods and at steady-state, week 12 for the first dosing period and week 36 for the second dosing period. | TFV-DP concentrations in DBS respective to dosing regimens of 33%, 67%, 100% of daily dosing. |
Countries
United States
Participant flow
Pre-assignment details
52 subjects from 2 sites were analyzed-- CU enrolled only 34.
Participants by arm
| Arm | Count |
|---|---|
| All Dosing Regimens Baseline characteristics for all 48 subjects included in analysis. Baseline characteristics not stratified based on dosing regimen. | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Dosing Regimens |
|---|---|
| Age, Continuous | 29 years |
| Race/Ethnicity, Customized Black/African American | 8 Participants |
| Race/Ethnicity, Customized Hispanic | 14 Participants |
| Race/Ethnicity, Customized White | 26 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 48 |
| other Total, other adverse events | 48 / 48 |
| serious Total, serious adverse events | 1 / 48 |
Outcome results
Primary
Steady State Concentrations of TFV-DP for Different Dosing Patterns of Truvada
TFV-DP concentrations in DBS respective to dosing regimens of 33%, 67%, 100% of daily dosing.
Time frame: Assessed every 2 weeks during the dosing periods and at steady-state, week 12 for the first dosing period and week 36 for the second dosing period.
Population: The total number of participants was 48. Each participant was randomized to 2 of 3 dosing regimens for a total of 32 participants each, however 2 participants completed only the first regimen.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DOT-DBS Dosing 33% | Steady State Concentrations of TFV-DP for Different Dosing Patterns of Truvada | 530 fmol/punch | Standard Deviation 159 |
| DOT-DBS Dosing 67% | Steady State Concentrations of TFV-DP for Different Dosing Patterns of Truvada | 997 fmol/punch | Standard Deviation 267 |
| DOT-DBS Dosing 100% | Steady State Concentrations of TFV-DP for Different Dosing Patterns of Truvada | 1605 fmol/punch | Standard Deviation 405 |