HIV/AIDS
Conditions
Keywords
HIV/AIDS, Adherence, Tenofovir, Dried Blood Spots
Brief 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.
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.
Interventions
None listed
Sponsors
University of Colorado, Denver
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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 | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Cohort 807 persons living with HIV (PLWH) on tenofovir disoproxil fumarate (TDF) at baseline were followed for up to three visits or 48 weeks. | 807 |
| Total | 807 |
Baseline characteristics
| Characteristic | Study Cohort |
|---|---|
| Age, Continuous | 46 years |
| Race/Ethnicity, Customized Race/Ethnicity Black | 149 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 147 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other | 39 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White | 472 Participants |
| Sex: Female, Male Female | 126 Participants |
| Sex: Female, Male Male | 681 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
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
Time frame: Up to 48 Weeks
Population: Drug concentrations were available from 532 participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Cohort | 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 | 73.5 Adjusted odds ratio (aOR) |
p-value: <0.000195% CI: [25.7, 210.5]Regression, Logistic
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
Time frame: Up to 48 Weeks
Population: Paired drug concentration (TFV-DP) and HIV VL assessments were available from 451 participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Cohort | 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 | 4.7 Adjusted odds ratio (aOR) |
p-value: <0.000195% CI: [2.6, 8.7]Regression, Logistic
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
Time frame: Up to 48 Weeks
Population: Three-month self-reported adherence data were available from 482 participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Cohort | Adjusted Odds Ratio of Three-month Self-reported Adeherence Associated With Odds of HIV Viral Suppression at All Study Visits | 8.5 Adjusted odds ratio (aOR) |
p-value: 0.001295% CI: [2.3, 30.9]Regression, Logistic