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.

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Key information

Conditions

HIV/AIDS Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Colorado-Anschutz Medical Campus

Aurora, Colorado, 80045, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

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

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Registry information

Official study title

Quantifying Drug Adherence and Drug Exposure to Antiretroviral Therapy.

Acronym: 2104

Important dates

Study start: 2013
Primary completion: 2017
Study completion: 2017
First posted: Dec 16, 2013
Registry last updated: Nov 25, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed