Quantifying Drug Adherence and Drug Exposure to Antiretroviral Therapy

HIV/AIDS Clinical Trial

— 2104  

Official title:

Quantifying Drug Adherence and Drug Exposure to Antiretroviral Therapy.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02012621
• Other study ID #: 13-2104
• Status: Completed
• Start date: December 2013
• Est. completion date: July 2017

Study information

• Verified date: October 2019
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. The investigators hypothesize that TFV-DP levels will be lowest in individuals with a detectable viral load and highest in those with viral suppression.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 807
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-infected individual.

• 18 years and older.

• Taking tenofovir.

• Blood drawn during regular clinic visit.

Exclusion Criteria:

• Refusal to participate.

• Pregnancy.

• Inability to provide informed consent.

Related Conditions & MeSH terms

• HIV/AIDS

Locations

Country	Name	City	State
United States	University of Colorado-Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 48 Weeks
Primary	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	Up to 48 Weeks
Primary	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	Up to 48 Weeks