title: Impact of disease, drug and patient adherence on the effectiveness of antiviral therapy in pediatric HIV.
abstract: Maintaining effective antiretroviral treatment for life is a major problem in both resource-limited and resource-rich countries. Despite the progress observed in paediatric antiretroviral therapy, approximately 12% of children still experience treatment failure due to drug resistance, inadequate dosing and poor adherence. We explore the current status of antiretroviral therapy in children with focus on the interaction between disease, drug pharmacokinetics and patient behavior, 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 scrutinized. A detailed assessment of factors affecting adherence is presented together with the main strategies to enhance treatment response in children. Expert opinion: Using modeling and simulation, a framework for characterizing the forgiveness of non-adherence for specific antiretroviral drugs in children is proposed in which information on pharmacokinetics, pharmacokinetic-pharmacodynamic relationships and viral dynamics is integrated. This approach represents an opportunity for the simplification of dosing regimens taking into account the interaction between these factors. Based on clinical trial simulation scenarios, we envisage the possibility of assessing the impact of variable adherence to antiretroviral drug combinations in HIV-infected children.
authors.affiliation: a Division of Pharmacology, Leiden Academic Centre for Drug Research , Leiden University , Leiden , The Netherlands.
authors.forename: Chiara
authors.initials: C
authors.lastname: Piana
authors.affiliation: a Division of Pharmacology, Leiden Academic Centre for Drug Research , Leiden University , Leiden , The Netherlands.
authors.forename: Meindert
authors.initials: M
authors.lastname: Danhof
authors.affiliation: b Clinical Pharmacology Modelling & Simulation , GlaxoSmithKline , Uxbridge , United Kingdom.|c Clinical Pharmacology & Therapeutics Group , University College London , London , United Kingdom.
authors.forename: Oscar
authors.initials: O
authors.lastname: Della Pasqua
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D055118:Medication Adherence; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents
keywords: PKPD modeling; Pediatric HIV; adherence; antiretroviral; clinical trial simulations; dose rationale; forgiveness; viral dynamics