Molecular Biotechnology

, Volume 58, Issue 1, pp 56–64

Low-Cost Method to Monitor Patient Adherence to HIV Antiretroviral Therapy Using Multiplex Cathepsin Zymography

  • Manu O. Platt
  • Denise Evans
  • Philip M. Keegan
  • Lynne McNamara
  • Ivana K. Parker
  • LaDeidra M. Roberts
  • Alexander W. Caulk
  • Rudolph L. GleasonJr.
  • Daniel Seifu
  • Wondwossen Amogne
  • Clement Penny
Original Paper

DOI: 10.1007/s12033-015-9903-0

Cite this article as:
Platt, M.O., Evans, D., Keegan, P.M. et al. Mol Biotechnol (2016) 58: 56. doi:10.1007/s12033-015-9903-0

Abstract

Monitoring patient adherence to HIV antiretroviral therapy (ART) by patient survey is inherently error prone, justifying a need for objective, biological measures affordable in low-resource settings where HIV/AIDS epidemic is highest. In preliminary studies conducted in Ethiopia and South Africa, we observed loss of cysteine cathepsin activity in peripheral blood mononuclear cells of HIV-positive patients on ART. We optimized a rapid protocol for multiplex cathepsin zymography to quantify cysteine cathepsins, and prospectively enrolled 350 HIV-positive, ART-naïve adults attending the Themba Lethu Clinic, Johannesburg, South Africa, to test if suppressed cathepsin activity could be a biomarker of ART adherence (103 patients were included in final analysis). Poor adherence was defined as detectable viral load (>400 copies/ml) or simplified medication adherence questionnaire, 4–6 months after ART initiation. 86 % of patients with undetectable viral loads after 6 months were cathepsin negative, and cathepsin-positive patients were twice as likely to have detectable viral loads (RR 2.32 95 % CI 1.26–4.29). Together, this demonstrates proof of concept that multiplex cathepsin zymography may be an inexpensive, objective method to monitor patient adherence to ART. Low cost of this electrophoresis-based assay makes it a prime candidate for implementation in resource-limited settings.

Keywords

Monitoring Zymography Cysteine protease Infectious disease AIDS Sub-Saharan Africa 

Abbreviations

3TC

Lamivudine

ART

Antiretroviral therapy

ARV

Antiretrovirals

CI

Confidence interval

EFV

Efavirenz

HIV

Human Immunodeficiency Virus

cART

Combination active antiretroviral therapy

LC/MS

Liquid chromatography–tandem mass spectroscopy

LPV/r

Lopinavir boosted with ritonavir

NNRTI

Non-nucleoside reverse transcriptase inhibitors

NRTI

Nucleoside reverse transcriptase inhibitors

NVP

Nevirapine

PBMC

Peripheral blood mononuclear cells

PI

Protease inhibitors

PrEP

Pre-exposure prophylaxis

RR

Risk ratio

SMAQ

Simplified medication adherence questionnaire

TDF

Tenofovir disoproxil fumarate

WHO

World Health Organization

Funding information

Funder NameGrant NumberFunding Note
Office of AIDS Research (US)
  • 5P30A1027767
NIH Office of the Director (US)
  • DP2OD007433
United States Agency for International Development (US)
  • 674-A-12-00029
American Heart Association (US)

    Copyright information

    © Springer Science+Business Media New York 2015

    Authors and Affiliations

    • Manu O. Platt
      • 1
      • 2
    • Denise Evans
      • 3
    • Philip M. Keegan
      • 1
      • 2
    • Lynne McNamara
      • 4
    • Ivana K. Parker
      • 2
      • 5
    • LaDeidra M. Roberts
      • 1
      • 2
    • Alexander W. Caulk
      • 2
      • 5
    • Rudolph L. GleasonJr.
      • 1
      • 2
      • 5
    • Daniel Seifu
      • 6
    • Wondwossen Amogne
      • 7
    • Clement Penny
      • 8
    1. 1.Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of Technology and Emory UniversityAtlantaUSA
    2. 2.The Petit Institute for Bioengineering and BioscienceGeorgia Institute of TechnologyAtlantaUSA
    3. 3.Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical MedicineUniversity of the WitwatersrandJohannesburgSouth Africa
    4. 4.Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical MedicineUniversity of the WitwatersrandJohannesburgSouth Africa
    5. 5.The George W. Woodruff School of Mechanical EngineeringAtlantaUSA
    6. 6.Department of BiochemistryAddis Ababa UniversityAddis AbabaEthiopia
    7. 7.Department of Internal MedicineAddis Ababa UniversityAddis AbabaEthiopia
    8. 8.Oncology Division, Department of Internal MedicineUniversity of the WitwatersrandJohannesburgSouth Africa

    Personalised recommendations