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

Ameya R. Kirtane(Massachusetts Institute of Technology), Omar Abouzid(Institut National des Sciences Appliquées de Lyon), Daniel Minahan(Massachusetts Institute of Technology), Taylor Bensel(Massachusetts Institute of Technology), Alison L. Hill(Harvard University), Christian Selinger(Bellevue Hospital Center), Anna Bershteyn(Bellevue Hospital Center), Morgan Craig(Harvard University), Shirley Mo(Harvard University), Hormoz Mazdiyasni(Massachusetts Institute of Technology), Cody Cleveland(Brigham and Women's Hospital), Jaimie Rogner(Massachusetts Institute of Technology), Young‐Ah Lucy Lee(Massachusetts Institute of Technology), Lucas Booth(Massachusetts Institute of Technology), Farhad Javid, Sarah J. Wu(Massachusetts Institute of Technology), Tyler M. Grant(Lyndra Therapeutics (United States)), Andrew M. Bellinger(Lyndra Therapeutics (United States)), Boris Nikolic, Alison Hayward(Massachusetts Institute of Technology), Lowell Wood(Bellevue Hospital Center), Philip A. Eckhoff(Bellevue Hospital Center), Martin A. Nowak(Harvard University), Róbert Langer(Massachusetts Institute of Technology), Giovanni Traverso(Brigham and Women's Hospital)
Nature Communications
December 27, 2017
Cited by 226Open Access
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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.


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