Use of Antiretroviral (ARV) Drug Levels in Dried Blood Spots (DBS) to Assess and Manage ART Adherence in South Africa

Study Overview
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Brief Summary
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This is a prospective, pilot study of HIV-positive individuals who have been on tenofovir-containing antiretroviral therapy for at least 4 months. The overall goal of this research is to determine the feasibility of giving patients and their providers monthly feedback about Tenofovir-Diphosphate (TFV-DP) drug levels and to examine patient and provider behaviors in response to receiving this information. This study will build upon the Aim 1 observational study and the subsequent patient and providerFeedback Development Workgroups (FDWs).

Detailed Description
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This is a prospective, pilot study of HIV-positive individuals who have been on tenofovir-containing antiretroviral therapy for at least 4 months. The overall goal of this research is to determine the feasibility of giving patients and their providers monthly feedback about Tenofovir-Diphosphate (TFV-DP) drug levels and to examine patient and provider behaviors in response to receiving this information. This study will build upon the Aim 1 observational study and the subsequent patient and provider Feedback Development Workgroups (FDWs). The study team will consent a sample (N=60) of HIV-positive patients for monthly assessments, including blood specimen collections to assess TFV-DP drug levels. Participants enrolled in this prospective, pilot study will be randomized to either the intervention arm in which they will receive monthly feedback on their TFV-DP drug levels (Feedback Group; N=30) or the control arm in which they will receive no feedback on TFV-DP drug levels (No Feedback Group; N=30). The study will take place at the Gugulethu Research Offices (GRO) of the Desmond Tutu HIV Foundation (DTHF) in Gugulethu, 15km outside Cape Town, South Africa (SA). Study participants will be recruited from patients attending one of four public-sector ART clinics in the Klipfontein Health District, Western Cape, including (1) Hannan Crusaid Treatment Centre, (2) Nyanga Clinic, (3) Gugulethu Clinic (NY1), and (4) Vuyani Clinic. Enrollment will occur over 3-4 months, during which study staff will recruit an average of 15-20 participants per month, for a total of 60 participants. Participants will remain in the study for 5 months, attending a baseline and 4 subsequent monthly study visits. At each monthly visit, study staff will obtain venous blood samples for dried blood spots (DBS) which will measure TFV-DP levels and a viral load (VL) assay. ART adherence will also be assessed through the Wise Pill electronic monitoring device (EMD) a medication dispenser that sends an electronic medication event record to the Wisepill server when medication is taken and monthly self-reported medication adherence. Socio-demographic characteristics, medical history, mental health, substance use, and other contextual factors will be assessed at baseline and at the final study visit. In addition, at each visit, participants randomized to the intervention arm will receive feedback on their previous month's TFV-DP drug levels. Clinic providers will also receive TFV-DP drug level results for the participants in the intervention arm. For both intervention and control groups, the study will monitor any changes to ART adherence behavior on the part of patients and providers. Potential changes will be monitored by reviewing participants' clinic charts to determine if any actions were made to the medical or adherence management of patients since the previous visit (e.g., additional VL requests beyond those prescribed for a stable patient, referral for intensive counselor-based or group adherence counseling, outreach by Health Care Workers (HCWs) for adherence monitoring and support, additional doctor-requested patient appointments). The study will also conduct Exit Interviews with participants and hold Provider Focus Group Discussions (FGD) to further understand whether (and if so, how) TFV-DP drug level feedback influenced medication adherence and patient management.

Official Title
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Use of ARV Drug Levels in Dried Blood Spots to Assess and Manage ART Adherence in South Africa

Conditions
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Therapeutic Adherence and Compliance

Intervention / Treatment
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* Behavioral: Feedback on DBS Concentrations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older HIV-positive Initiated ARV's containing tenofovir 4 or more months ago Speaks English or Xhosa Willing to attend 5 study visits approximately one month apart Willing to allow the study team to contact his/her HIV care provider about his/her monthly TFV-diphosphate (TFV-DP) drug level Willing to use Wise Pill to dispense ARVs for 4 months Willing to receive text/short message service (SMS) and/or phone call reminders to charge the Wise Pill Willing to allow the study team access to their medical chart/clinic folder Exclusion Criteria: Unable to provide informed consent Unwilling to participate in study procedures Unwilling to allow the study team to contact his/her HIV care provider about his/her monthly TFV-DP drug level Any condition that, in the opinion of the principal investigator would make participation in the study unsafe, complicated interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Receiving Feedback From DBS<br>This arm of participants will receive monthly feedback from medical providers on their adherence measured through DBS. | Behavioral: Feedback on DBS Concentrations<br>* The study team will examine the feasibility and acceptability of a feedback system based on DBS concentration amounts.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TFV-diphosphate (TFV-DP) Drug Level | Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is used as a biomarker of antiretroviral therapy (ART) adherence. Recent treatment studies have shown that TFV-DP predicts future viremia in persons with HIV (PWH). Whole blood for DBS was collected at each study visit by venipuncture. To prepare the DBS, 25 mcl of whole blood were spotted five times onto a Whatman 903 ProteinSaver card and dried for a minimum of 3hrs and up to overnight before being individually packaged in a plastic bag with dessicant and a humidity indicator. | 5 Months | 
| Viral Load (VL) Assay |  | 5 months | 
| Electronic Adherence (EA) Percentages | The number of days recorded as intake on electronic medical device (EMD) divided by days on study | 5 months |