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

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

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).

Study Overview

• Status: Completed
• Conditions: Therapeutic Adherence and Compliance
• Intervention / Treatment: Behavioral: Feedback on DBS Concentrations

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7750
      • Gugulethu Clinic
• United States
  • New York
    • New York, New York, United States, 10032
      • 1051 Riverside Drive

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: University of Colorado, Denver; National Institute of Allergy and Infectious Diseases (NIAID); Research Foundation for Mental Hygiene, Inc.; University of Cape Town; Desmond Tutu HIV Foundation
• Investigators: Principal Investigator: Robert H Remien, Ph.D, NY State Psychiatric Institute: Columbia University Department of Psychiatry, College of Physicians and Surgeons; Principal Investigator: Catherine Orrell, Ph.D MBChB, Desmond Tutu HIV Centre/Foundation: University of Cape Town

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2020
• Primary Completion (Actual): December 15, 2021
• Study Completion (Actual): November 29, 2022

Study Registration Dates

• First Submitted: April 1, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 3, 2020

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 7213 (Other Identifier: CTEP); R01AI122300 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No