Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy

Ameya R. Kirtane, Omar Abouzid, Daniel Minahan, Taylor Bensel, Alison L. Hill, Christian Selinger, Anna Bershteyn, Morgan Craig, Shirley S. Mo, Hormoz Mazdiyasni, Cody Cleveland, Jaimie Rogner, Young-Ah Lucy Lee, Lucas Booth, Farhad Javid, Sarah J. Wu, Tyler Grant, Andrew M. Bellinger, Boris Nikolic, Alison Hayward, Lowell Wood, Philip A. Eckhoff, Martin A. Nowak, Robert Langer () and Giovanni Traverso ()
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Ameya R. Kirtane: Massachusetts Institute of Technology
Omar Abouzid: Massachusetts Institute of Technology
Daniel Minahan: Massachusetts Institute of Technology
Taylor Bensel: Massachusetts Institute of Technology
Alison L. Hill: Harvard University
Christian Selinger: Institute for Disease Modeling
Anna Bershteyn: Institute for Disease Modeling
Morgan Craig: Harvard University
Shirley S. Mo: Harvard University
Hormoz Mazdiyasni: Massachusetts Institute of Technology
Cody Cleveland: Massachusetts Institute of Technology
Jaimie Rogner: Massachusetts Institute of Technology
Young-Ah Lucy Lee: Massachusetts Institute of Technology
Lucas Booth: Massachusetts Institute of Technology
Sarah J. Wu: Massachusetts Institute of Technology
Tyler Grant: Lyndra Inc
Andrew M. Bellinger: Lyndra Inc
Boris Nikolic: Biomatics Capital
Alison Hayward: Massachusetts Institute of Technology
Lowell Wood: Institute for Disease Modeling
Philip A. Eckhoff: Institute for Disease Modeling
Martin A. Nowak: Harvard University
Robert Langer: Massachusetts Institute of Technology
Giovanni Traverso: Massachusetts Institute of Technology

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug–polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide.

Date: 2018
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DOI: 10.1038/s41467-017-02294-6

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