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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Anti-HIV Agents / administration & dosage*
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Anti-HIV Agents / pharmacokinetics
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Anti-HIV Agents / therapeutic use
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Drug Delivery Systems / methods*
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Drug Evaluation, Preclinical
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Heterocyclic Compounds, 3-Ring / administration & dosage*
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Heterocyclic Compounds, 3-Ring / pharmacokinetics
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Heterocyclic Compounds, 3-Ring / therapeutic use
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Humans
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Models, Theoretical
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Oxazines
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Patient Compliance
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Piperazines
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Proof of Concept Study
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Pyridones / administration & dosage*
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Pyridones / pharmacokinetics
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Pyridones / therapeutic use
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Rilpivirine / administration & dosage*
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Rilpivirine / pharmacokinetics
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Rilpivirine / therapeutic use
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Swine
Substances
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Anti-HIV Agents
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Heterocyclic Compounds, 3-Ring
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Oxazines
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Piperazines
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Pyridones
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dolutegravir
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Rilpivirine
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cabotegravir