HIV/AIDS2104NCT02012621
Quantifying Drug Adherence and Drug Exposure to Antiretroviral Therapy
An observational study of HIV/AIDS, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The purpose of this study is to evaluate cumulative exposure to tenofovir diphosphate (TFV-DP) using dried blood spots (DBS) in treated HIV-infected patients who are receiving a TFV-based regimen. Using DBS will allow the investigators to assess this simple method to measure drug exposure in the clinical setting. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV/AIDS
- How many people
- 807 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to Jul 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HIV-infected individuals who are taking tenofovir.
Who may be able to join
- HIV-infected individual.
- 18 years and older.
- Taking tenofovir.
- Blood drawn during regular clinic visit.
Who cannot join
- Refusal to participate.
- Pregnancy.
- Inability to provide informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado-Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
Official title: Quantifying Drug Adherence and Drug Exposure to Antiretroviral Therapy.
The purpose of this study is to evaluate cumulative exposure to tenofovir diphosphate (TFV-DP) using dried blood spots (DBS) in treated HIV-infected patients who are receiving a TFV-based regimen. Using DBS will allow the investigators to assess this simple method to measure drug exposure in the clinical setting. The investigators hypothesize that TFV-DP levels will be lowest in individuals with a detectable viral load and highest in those with viral suppression.
Read the detailed description
Antiretroviral drug exposure is directly linked to individual host factors which include age, weight, diet, and genetics. However, the main factor impacting long-term drug exposure is drug adherence. Adherence is a strong predictor of HIV treatment outcomes, but measuring adherence is difficult due to the inaccuracy of self-reporting and other commonly used monitoring methods. To date, no gold standard measure to monitor antiretroviral exposure and adherence has been applied in clinical practice. Tenofovir (TFV) and its active metabolite, tenofovir diphosphate (TFV-DP), have distinctive pharmacological characteristics that make them ideal candidates for drug adherence and exposure monitoring. The long half life (~14-17 days) of TFV-DP in red blood cells (RBC) are properties well suited for monitoring average dose exposure over time. Based on these, the investigators propose that RBC levels of TFV-DP are an accurate and precise measure of long-term drug exposure in HIV-infected individuals. In addition, the investigators aim to quantify TFV-DP in dried blood spots (DBS) as a simple method to measure drug exposure.
This is an observational, 48-week prospective study of HIV-infected individuals treated with TFV in which the investigators will compare DBS TFV-DP levels in virologically suppressed vs. non-suppressed individuals and evaluate the utility of TFV-DP in DBS to predict virologic failure and also drug toxicity. To accomplish this, the investigators will approach HIV-infected patients currently taking TFV (which is being prescribed by a primary care physician) and who present to the clinic for regular HIV care. After informed consent is obtained, the investigators will collect extra blood samples for DBS TFV-DP and obtain information on drug adherence. The investigators will also collect extra blood samples for DBS TFV-DP at each subject's subsequent visit for approximately 3 visits in a 48 week period of time.
- Conditions
- HIV/AIDS
- Keywords
- HIV/AIDS, Adherence, Tenofovir, Dried Blood Spots
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What is being measured
The primary outcome is the main question the study is designed to answer.
Adjusted Odds Ratio of Level of Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS) Associated With Odds of HIV Viral Suppression at All Study Visits
HIV viral load, binary cutoff at assay level of detection (<20 copies/mL vs. >= 20 copies/mL); reference group: drug concentration (TFV-DP) < 350 femtomole (fmol)/punch vs. drug concentration (TFV-DP) >= 1850 fmol/punch; adjusted odds ratio calculated using generalized estimating equations; concentration cutoffs established in prior research of healthy volunteers
Measured: Up to 48 Weeks
Adjusted Odds Ratio of Three-month Self-reported Adeherence Associated With Odds of HIV Viral Suppression at All Study Visits
HIV viral load, binary cutoff at assay level of detection (<20 copies/mL vs. >= 20 copies/mL); reference group: three-month self-reported adherence <28.5% vs. three-month self-reported adherence 100%; adherence cutoffs established in prior research
Measured: Up to 48 Weeks
Adjusted Odds Ratio of Level of Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS) Associated With Odds of HIV Viral Suppression at Next Study Visit
HIV viral load, binary cutoff at assay level of detection (<20 copies/mL vs. >= 20 copies/mL); drug concentration (TFV-DP) <800 femtomole (fmol)/punch) vs reference group of drug concentration (TFV-DP) >= 1650 fmol/punch; adjusted odds ratio calculated using generalized estimating equations
Measured: Up to 48 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2013 (estimated)
- Study startDec 2013
- Primary completionJul 2017
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 807 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jose R. Castillo-Mancilla, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012621
- Sponsor's protocol ID
- 13-2104
- Acronym
- 2104
- Status last verified
- Oct 2019
- First submitted
- 4 Dec 2013
- Last updated
- 25 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Morrow M, MaWhinney S, Coyle RP, Coleman SS, Gardner EM, Zheng JH, Ellison L, Bushman LR, Kiser JJ, Anderson PL, Castillo-Mancilla JR. Predictive Value of Tenofovir Diphosphate in Dried Blood Spots for Future Viremia in Persons Living With HIV. J Infect Dis. 2019 Jul 19;220(4):635-642. doi: 10.1093/infdis/jiz144.
PubMed 30942881Castillo-Mancilla JR, Morrow M, Coyle RP, Coleman SS, Gardner EM, Zheng JH, Ellison L, Bushman LR, Kiser JJ, Mawhinney S, Anderson PL. Tenofovir Diphosphate in Dried Blood Spots Is Strongly Associated With Viral Suppression in Individuals With Human Immunodeficiency Virus Infections. Clin Infect Dis. 2019 Apr 8;68(8):1335-1342. doi: 10.1093/cid/ciy708.
PubMed 30137238Castillo-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.
PubMed 27572401
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantifying Drug Adherence and Drug Exposure to Antiretroviral Therapy.
- ClinicalTrials.gov ID
- NCT02012621
- Acronym / sponsor ID
- 2104 / 13-2104
- Conditions
- HIV/AIDS
- Keywords
- HIV/AIDS, Adherence, Tenofovir, Dried Blood Spots
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 807 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 16 Dec 2013 (estimated)
- Results
- Posted 25 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate cumulative exposure to tenofovir diphosphate (TFV-DP) using dried blood spots (DBS) in treated HIV-infected patients who are receiving a TFV-based regimen. Using DBS will allow the investigators to assess this simple method to measure drug exposure in the clinical setting. The investigators hypothesize that TFV-DP levels will be lowest in individuals with a detectable viral load and highest in those with viral suppression.
Detailed description
Antiretroviral drug exposure is directly linked to individual host factors which include age, weight, diet, and genetics. However, the main factor impacting long-term drug exposure is drug adherence. Adherence is a strong predictor of HIV treatment outcomes, but measuring adherence is difficult due to the inaccuracy of self-reporting and other commonly used monitoring methods. To date, no gold standard measure to monitor antiretroviral exposure and adherence has been applied in clinical practice. Tenofovir (TFV) and its active metabolite, tenofovir diphosphate (TFV-DP), have distinctive pharmacological characteristics that make them ideal candidates for drug adherence and exposure monitoring. The long half life (~14-17 days) of TFV-DP in red blood cells (RBC) are properties well suited for monitoring average dose exposure over time. Based on these, the investigators propose that RBC levels of TFV-DP are an accurate and precise measure of long-term drug exposure in HIV-infected individuals. In addition, the investigators aim to quantify TFV-DP in dried blood spots (DBS) as a simple method to measure drug exposure.
This is an observational, 48-week prospective study of HIV-infected individuals treated with TFV in which the investigators will compare DBS TFV-DP levels in virologically suppressed vs. non-suppressed individuals and evaluate the utility of TFV-DP in DBS to predict virologic failure and also drug toxicity. To accomplish this, the investigators will approach HIV-infected patients currently taking TFV (which is being prescribed by a primary care physician) and who present to the clinic for regular HIV care. After informed consent is obtained, the investigators will collect extra blood samples for DBS TFV-DP and obtain information on drug adherence. The investigators will also collect extra blood samples for DBS TFV-DP at each subject's subsequent visit for approximately 3 visits in a 48 week period of time.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HIV-infected individuals who are taking tenofovir.
Key inclusion criteria (4 listed)
- HIV-infected individual.
- 18 years and older.
- Taking tenofovir.
- Blood drawn during regular clinic visit.
Key exclusion criteria (3 listed)
- Refusal to participate.
- Pregnancy.
- Inability to provide informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Adjusted Odds Ratio of Level of Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS) Associated With Odds of HIV Viral Suppression at All Study Visits
Time frame: Up to 48 Weeks
HIV viral load, binary cutoff at assay level of detection (<20 copies/mL vs. >= 20 copies/mL); reference group: drug concentration (TFV-DP) < 350 femtomole (fmol)/punch vs. drug concentration (TFV-DP) >= 1850 fmol/punch; adjusted odds ratio calculated using generalized estimating equations; concentration cutoffs established in prior research of healthy volunteers
Adjusted Odds Ratio of Three-month Self-reported Adeherence Associated With Odds of HIV Viral Suppression at All Study Visits
Time frame: Up to 48 Weeks
HIV viral load, binary cutoff at assay level of detection (<20 copies/mL vs. >= 20 copies/mL); reference group: three-month self-reported adherence <28.5% vs. three-month self-reported adherence 100%; adherence cutoffs established in prior research
Adjusted Odds Ratio of Level of Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS) Associated With Odds of HIV Viral Suppression at Next Study Visit
Time frame: Up to 48 Weeks
HIV viral load, binary cutoff at assay level of detection (<20 copies/mL vs. >= 20 copies/mL); drug concentration (TFV-DP) <800 femtomole (fmol)/punch) vs reference group of drug concentration (TFV-DP) >= 1650 fmol/punch; adjusted odds ratio calculated using generalized estimating equations
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30942881Morrow M, MaWhinney S, Coyle RP, Coleman SS, Gardner EM, Zheng JH, Ellison L, Bushman LR, Kiser JJ, Anderson PL, Castillo-Mancilla JR. Predictive Value of Tenofovir Diphosphate in Dried Blood Spots for Future Viremia in Persons Living With HIV. J Infect Dis. 2019 Jul 19;220(4):635-642. doi: 10.1093/infdis/jiz144.
- Derived from this study: PubMed 30137238Castillo-Mancilla JR, Morrow M, Coyle RP, Coleman SS, Gardner EM, Zheng JH, Ellison L, Bushman LR, Kiser JJ, Mawhinney S, Anderson PL. Tenofovir Diphosphate in Dried Blood Spots Is Strongly Associated With Viral Suppression in Individuals With Human Immunodeficiency Virus Infections. Clin Infect Dis. 2019 Apr 8;68(8):1335-1342. doi: 10.1093/cid/ciy708.
- Derived from this study: PubMed 27572401Castillo-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jose R. Castillo-Mancilla, MD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV/AIDS, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adjusted Odds Ratio of Level of Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS) Associated With Odds of HIV Viral Suppression at All Study Visits (time frame: Up to 48 Weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02012621, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2019; AzTrials last refreshed its copy on 8 Nov 2026.