title: Low-Cost Method to Monitor Patient Adherence to HIV Antiretroviral Therapy Using Multiplex Cathepsin Zymography.
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.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive, IBB 1308, Atlanta, GA, 30332, USA. manu.platt@bme.gatech.edu.|The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA. manu.platt@bme.gatech.edu.
authors.forename: Manu O
authors.initials: MO
authors.lastname: Platt
authors.affiliation: Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Denise
authors.initials: D
authors.lastname: Evans
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive, IBB 1308, Atlanta, GA, 30332, USA.|The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Keegan
authors.affiliation: Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Lynne
authors.initials: L
authors.lastname: McNamara
authors.affiliation: The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.|The George W. Woodruff School of Mechanical Engineering, Atlanta, GA, USA.
authors.forename: Ivana K
authors.initials: IK
authors.lastname: Parker
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive, IBB 1308, Atlanta, GA, 30332, USA.|The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: LaDeidra M
authors.initials: LM
authors.lastname: Roberts
authors.affiliation: The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.|The George W. Woodruff School of Mechanical Engineering, Atlanta, GA, USA.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Caulk
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive, IBB 1308, Atlanta, GA, 30332, USA.|The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.|The George W. Woodruff School of Mechanical Engineering, Atlanta, GA, USA.
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Gleason
authors.affiliation: Department of Biochemistry, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Seifu
authors.affiliation: Department of Internal Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Wondwossen
authors.initials: W
authors.lastname: Amogne
authors.affiliation: Oncology Division, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Clement
authors.initials: C
authors.lastname: Penny
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D002403:Cathepsins / Q000097:blood / Q000235:genetics*; D003362:Cost-Benefit Analysis; D003545:Cysteine / Q000235:genetics; D004586:Electrophoresis; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D055118:Medication Adherence; D013019:South Africa; D019562:Viral Load
chemical_list: D002403:Cathepsins; D003545:Cysteine
keywords: AIDS; Cysteine protease; Infectious disease; Monitoring; Sub-Saharan Africa; Zymography