Clinical trial NCT02022657: Pre-Exposure Prophylaxis (PrEP) Adherence Monitoring Using Dried Blood Spots
Official title: PrEP Adherence Monitoring Using Dried Blood Spots
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: PrEP Adherence Monitoring
Keywords: Pre exposure prophylaxis
Dried blood spots
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: San Francisco Department of Public Health
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2013-12-30
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Steady State Concentrations of TFV-DP for Different Dosing Patterns of Truvada
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco/San Francisco Department of Public Health
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Peter L Anderson, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Anderson PL, Liu AY, Castillo-Mancilla JR, Gardner EM, Seifert SM, McHugh C, Wagner T, Campbell K, Morrow M, Ibrahim M, Buchbinder S, Bushman LR, Kiser JJ, MaWhinney S. Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots following Directly Observed Therapy. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01710-17. doi: 10.1128/AAC.01710-17. Print 2018 Jan.
citation: Ibrahim ME, Castillo-Mancilla JR, Yager J, Brooks KM, Bushman L, Saba L, Kiser JJ, MaWhinney S, Anderson PL. Individualized Adherence Benchmarks for HIV Pre-Exposure Prophylaxis. AIDS Res Hum Retroviruses. 2021 Jun;37(6):421-428. doi: 10.1089/AID.2020.0108. Epub 2020 Dec 10.
citation: Grant RM, Pellegrini M, Defechereux PA, Anderson PL, Yu M, Glidden DV, O'Neal J, Yager J, Bhasin S, Sevelius J, Deutsch MB. Sex Hormone Therapy and Tenofovir Diphosphate Concentration in Dried Blood Spots: Primary Results of the Interactions Between Antiretrovirals And Transgender Hormones Study. Clin Infect Dis. 2021 Oct 5;73(7):e2117-e2123. doi: 10.1093/cid/ciaa1160.
citation: Koss CA, Liu AY, Castillo-Mancilla J, Bacchetti P, McHugh C, Kuncze K, Morrow M, Louie A, Seifert S, Okochi H, MaWhinney S, Gandhi M, Anderson PL. Similar tenofovir hair concentrations in men and women after directly observed dosing of tenofovir disoproxil fumarate/emtricitabine: implications for preexposure prophylaxis adherence monitoring. AIDS. 2018 Sep 24;32(15):2189-2194. doi: 10.1097/QAD.0000000000001935.
citation: Castillo-Mancilla J, Seifert S, Campbell K, Coleman S, McAllister K, Zheng JH, Gardner EM, Liu A, Glidden DV, Grant R, Hosek S, Wilson CM, Bushman LR, MaWhinney S, Anderson PL. Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6692-6697. doi: 10.1128/AAC.01017-16. Print 2016 Nov.