Use of ARV Drug Levels in DBS to Assess and Manage ART Adherence in South Africa

Co-Investigator(s):

Reuben Robbins, PhD

Patricia Warne, PhD

Claude Mellins, PhD

Cheng-Shiun Leu, PhD

Peter L. Anderson, PharmD

José Castillo-Mancilla, MD

Landon Myer, MD, PhD

Anna Cross MBChB

John Joska, MBChB, PhD

Nadia Nguyen, MSPH

 

Funding Agency:

Division of Acquired Immunodeficiency Syndrome (DAIDS)

Collaborating Institution: 

Desmond Tutu HIV Foundation, University of Cape Town, South Africa

University of Colorado, Denver

Study Location:

Cape Town, South Africa

Description:

The overall aim of the ADD-ART study is to determine the utility of tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS) as an objective measure of adherence to antiretroviral treatment (ART) in South Africa. 

In years 1 through 3, we will:  

  1. compare the ability of the DBS TFV-DP assay and Wisepill (a pill box that sends a signal to a secure website whenever the device is opened as a proxy for ART adherence) to predict future viral breakthrough; 
     
  2. determine the magnitude of decrease in drug anabolite levels that predicts viral breakthrough and the lead-time to that breakthrough; and
     
  3. document the range of DBS-derived TFV-DP levels in South African patients who remain virally suppressed. 

In years 4 and 5, we will determine the appropriate and preferred methods for, and feasibility of, giving patients and providers monthly feedback about TFV-DP levels and examine provider and patient behaviors in response to receiving this information.

This prospective, observational cohort study is being conducted at the Gugulethu Research Offices (GRO) of the Desmond Tutu HIV Foundation (DTHF). We are currently recruiting 250 HIV-positive individuals who have recently initiated tenofovir-containing antiretroviral therapy and who are currently virally suppressed. Participants are followed for 12 months and provide monthly finger-prick and venous blood samples for DBS to measure TFV-DP and emtricitabine-triphosphate (FTC-TP) levels in red blood cells (RBCs). ART adherence is measured through continuous monitoring using the Wisepill electronic monitoring device (EMD) and monthly self-report. HIV-1 RNA VL and hematocrit are being measured monthly and at every other month, respectively. Participants who experience viral breakthrough are tested for antiretroviral (ARV) drug resistance. Socio-demographic characteristics, medical history, mental health, substance use, and other contextual factors are assessed at baseline and the final study visit. Acceptability of DBS sampling is assessed every other month, with more in-depth questions at the final visit.
 

Presentations/
Publications:

 

  • Robbins, R., Gouse, H.,  Mtingeni, Y., Lopez-Rios, J., Mellins, C., Joska, J., Warne, P. and Remien, R. Feasibility and Acceptability of Hair- and Dried Blood Spot-Derived ARV Biomarkers as Objective Measures of Treatment Adherence in South Africa: Oral Abstract, 10th International Conference on HIV Treatment Adherence, June 28-30, 2015, Miami, FL.

  • Warne, P., Robbins, R., Andersen, P., Gouse, H., Joska, J., Leu, C-S., Mtingeni, Y., Henry, M., Lopez-Rios, J., Castillo-Mancilla, J., Levin, B., Mellins, C. and Remien, R. Utility of Dried Blood Spot-Derived ARV Biomarkers as an Objective Measure of Treatment Adherence in South Africa: Oral Abstract, 10th International Conference on HIV Treatment Adherence, June 28-30, 2015, Miami, FL