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Nat Commun. 2018 Jan 9;9(1):2. doi: 10.1038/s41467-017-02294-6.

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

Author information

1
Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
2
Département Biosciences, Institut National des Sciences Appliquées de Lyon, 20 Avenue Albert Einstein, Villeurbanne, France, 69100.
3
Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, 02138, USA.
4
Institute for Disease Modeling, Bellevue, WA, 98005, USA.
5
Division of Gastroenterology Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
6
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
7
Lyndra Inc, Watertown, MA, 02472, USA.
8
Biomatics Capital, 1107 1st Avenue, Apartment 1305, Seattle, WA, 98101, USA.
9
Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. rlanger@mit.edu.
10
Media Lab, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. rlanger@mit.edu.
11
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. rlanger@mit.edu.
12
Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. ctraverso@bwh.harvard.edu.
13
Division of Gastroenterology Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. ctraverso@bwh.harvard.edu.

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.

PMID:
29317618
PMCID:
PMC5760734
DOI:
10.1038/s41467-017-02294-6
[Indexed for MEDLINE]
Free PMC Article

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