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Impact of disease, drug and patient adherence on the effectiveness of antiviral therapy in pediatric HIV

Piana, C; Danhof, M; Della Pasqua, O; (2017) Impact of disease, drug and patient adherence on the effectiveness of antiviral therapy in pediatric HIV. Expert Opinion on Drug Metabolism and Toxicology , 13 (5) pp. 497-511. 10.1080/17425255.2017.1277203. Green open access

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Abstract

INTRODUCTION: Maintaining effective antiretroviral treatment for life is a major problem, in both resource-limited and resource-rich countries. Despite the progresses observed in paediatric antiretroviral therapy, approximately 12% of children still experience treatment failure due to drug resistance, inadequate dosing and poor adherence. This review is aimed at exploring the current status of antiretroviral therapy in children with focus on the interaction between disease, drug pharmacokinetics and patient behaviour, all of which are strongly interconnected and determine treatment outcome. AREAS COVERED: An overview is provided of the viral characteristics and available drug combinations aimed at the prevention of resistance. In this context, the role of patient adherence is scrutinised. A detailed assessment of the factors affecting adherence is presented together with the main strategies to enhance treatment response in children. EXPERT OPINION: Using modelling and simulation, a framework for assessing the forgiveness of non-adherence for specific antiretroviral regimens in children is proposed in which information on pharmacokinetics (PK), pharmacokinetic-pharmacodynamic (PKPD) relationships and viral dynamics are integrated. This approach represents an opportunity for the simplification of dosing regimens taking into account the interaction between these factors. Based on clinical trial simulations, we envisage the possibility to assess the impact of variable adherence to antiretroviral drug combinations in HIV-infected children.

Type: Article
Title: Impact of disease, drug and patient adherence on the effectiveness of antiviral therapy in pediatric HIV
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/17425255.2017.1277203
Publisher version: http://dx.doi.org/10.1080/17425255.2017.1277203
Language: English
Additional information: Copyright © 2017 Taylor & Francis. This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Metabolism & Toxicology on 3 January 2017, available online: http://dx.doi.org/10.1080/17425255.2017.1277203
Keywords: pediatric HIV, antiretroviral, viral dynamics, adherence, dose rationale, forgiveness, PKPD modeling, clinical trial simulations
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1535256
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