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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.
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.
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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HIV-infected individuals who are taking tenofovir.
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| Name | Affiliation | Role |
|---|---|---|
| Jose R. Castillo-Mancilla, MD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado-Anschutz Medical Campus | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30942881 | Derived | 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. | |
| 30137238 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
TFV-DP concentrations in DBS were available from 532 participants over three visits or 48 weeks. TFV-DP concentrations in DBS were available from 521 participants at baseline. Demographics from the full cohort (N=807) are reported here.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Drug concentrations were available from 532 participants | Posted | Number | 95% Confidence Interval | Adjusted odds ratio (aOR) | Up to 48 Weeks |
|
N/A: observational study where samples were collected at the time of normally scheduled clinic visits
N/A: observational study where samples were collected at the time of normally scheduled clinic visits; AEs not assessed
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jose Castillo-Mancilla | University of Colorado-AMC | 303-724-4934 | jose.castillo-mancilla@cuanschutz.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 21, 2013 | Sep 13, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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Whole Blood
| Castillo-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. |
| 27572401 | Derived | 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. |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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 | Three-month self-reported adherence data were available from 482 participants | Posted | Number | 95% Confidence Interval | Adjusted odds ratio (aOR) | Up to 48 Weeks |
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| 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 | Paired drug concentration (TFV-DP) and HIV VL assessments were available from 451 participants | Posted | Number | 95% Confidence Interval | Adjusted odds ratio (aOR) | Up to 48 Weeks |
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| 0 |
| 0 |
| 0 |
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| 0 |
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| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |