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HIV-1 Sanctuary Sites—the Role of Membrane-Associated Drug Transporters and Drug Metabolic Enzymes

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  • Theme: Celebrating Women in the Pharmaceutical Sciences
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Abstract

Despite significant advances in the treatment of human immunodeficiency virus-1 (HIV) infection with highly active antiretroviral drug therapy, the persistence of the virus in cellular and anatomic reservoirs is a major obstacle preventing total HIV eradication. Viral persistence could result from a variety of contributing factors including, but not limited to, non-adherence to treatment and adverse drug reactions, latently infected cells carrying replication-competent virus, drug–drug interactions, and inadequate antiretroviral drug (ARV) concentrations reached in several anatomic sites such as the brain, testis, and gut-associated lymphoid tissues. The distribution of ARVs at specific sites of infection is primarily dependent on drug physicochemical properties and drug plasma protein binding, as well as drug efflux, influx, and metabolic processes. A thorough understanding of the functional roles of drug transporters and metabolic enzymes in the disposition of ARVs in immune cell types and tissues that are characterized as HIV reservoirs and sanctuaries is critical to overcome the challenge of suboptimal drug distribution at sites of persistent HIV infection. This review summarizes the current knowledge related to the expression and function of drug transporters and metabolic enzymes in HIV cellular and anatomic reservoirs, and their potential contribution to drug–drug interactions and insufficient drug concentration at these sites.

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Acknowledgments

This work is supported by an operating grant from the Canadian Institutes of Health Research (MOP-56976) and a University of Toronto, Leslie Dan Faculty of Pharmacy Internal Grant 202079 awarded to Dr. Reina Bendayan. Dr. Bendayan is a career scientist of the Ontario HIV Treatment Network (OHTN), Ministry of Health of Ontario. Ms. Sana-Kay Whyte-Allman is the recipient of the University of Toronto Connaught International Doctoral Scholarship.

Contribution by Authors as Women Scientists

Sana-Kay Whyte-Allman

Sana-Kay Whyte-Allman is a PhD student at the Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, where she is supervised by Dr. Reina Bendayan. Sana-Kay conducts research to investigate the role and regulation of membrane-associated drug transport proteins and drug metabolic enzymes in HIV antiretroviral drug disposition, and their potential contribution to persistent HIV infection. Her work has resulted in several first authorship and co-authored publications, international and national conference presentations, and travel scholarships. Sana-Kay is also a recipient of the prestigious University of Toronto Connaught International Doctoral Scholarship for the duration of her PhD studies. As an international student from Jamaica, Sana-Kay represents a first-generation college/university student from a minority group, and an accomplished young researcher with a strong desire to make significant contributions to the pharmaceutical science field.

Reina Bendayan

Dr. Reina Bendayan is a professor of the Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, and career scientist of the Ontario HIV Treatment Network, Ministry of Health of Ontario. Dr. Bendayan’s research program is primarily focused on Membrane Transport and Therapeutics with an emphasis in the field of HIV/AIDS Antiviral Drug Transport and Regulation at sanctuary sites and cellular reservoirs of HIV. Her research program is primarily funded by the Canadian Institutes of Health Research, Ministry of Health of Ontario, and the Natural Sciences and Engineering Research Council of Canada. She is the author of over 100 peer-reviewed manuscripts, and over the course of her academic career, she has supervised many undergraduate research students, master’s students, doctoral students, and post-doctoral research fellows. Dr. Bendayan understands the immense value of welcoming diversity into her laboratory and over the past years has put significant efforts in ensuring an inclusive research environment in her laboratory including men, women, and individuals from under-represented groups. Dr. Bendayan was elected Fellow of the AAPS (2010) and the Canadian Society of Pharmaceutical Sciences (CSPS, 2015), and received the Association of Faculties of Pharmacy of Canada Research Career Award (2013) and the CSPS Research Leadership Award (2019). She served as Graduate Chair and Associate Dean Graduate Education of the Graduate Department of Pharmaceutical Sciences (July 2005–July 2011) and as Acting Dean of the Leslie Dan Faculty of Pharmacy (January 2007–July 2007).

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  1. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario, M5S 3M2, Canada

    Sana-Kay Whyte-Allman & Reina Bendayan

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Whyte-Allman, SK., Bendayan, R. HIV-1 Sanctuary Sites—the Role of Membrane-Associated Drug Transporters and Drug Metabolic Enzymes. AAPS J 22, 118 (2020). https://doi.org/10.1208/s12248-020-00498-1

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