J Nuttall1, V Pillay2. 1. Paediatric Infectious Diseases Unit, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Rondebosch, Cape Town, 7700, South Africa. james.nuttall@uct.ac.za. 2. Paediatric Infectious Diseases Unit, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Rondebosch, Cape Town, 7700, South Africa.
Abstract
PURPOSE OF REVIEW: To provide an update on the patterns of HIV drug resistance in children, including pretreatment drug resistance (PDR) and acquired drug resistance (ADR), focusing on children in low- and middle-income countries (LMICs) for whom empiric first-line (FL) and second-line (SL) antiretroviral regimens are usually recommended. RECENT FINDINGS: High levels of PDR, particularly to non-nucleoside reverse transcriptase inhibitors (NNRTIs), and poor treatment outcomes on NNRTI-based FL antiretroviral therapy (ART) have been widely reported among infants and young children. There is a paucity of recent data on the use of protease inhibitor (PI)-based FL and SL regimens in children, but studies have reported poor tolerability, adherence problems and the development of PI resistance. Limited access to virological monitoring and HIV drug resistance testing contributes to delays in identifying treatment failure due to ADR and delays in switching to SL regimens in children. Implementation of FL ART regimens that have a higher barrier to developing resistance and are safe and well tolerated is required in order to attain global treatment targets. Although PI-based regimens may be effective as FL or SL treatment in children, lack of appropriate formulations leading to poor tolerability, drug-drug interactions, and cost considerations have negatively impacted their use among children in LMICs. There is hope that dolutegravir-based regimens recommended for children by the World Health Organization will be widely implemented once child-friendly formulations are available, and dosing and safety studies currently underway are completed, and that this will significantly improve treatment outcomes.
PURPOSE OF REVIEW: To provide an update on the patterns of HIV drug resistance in children, including pretreatment drug resistance (PDR) and acquired drug resistance (ADR), focusing on children in low- and middle-income countries (LMICs) for whom empiric first-line (FL) and second-line (SL) antiretroviral regimens are usually recommended. RECENT FINDINGS: High levels of PDR, particularly to non-nucleoside reverse transcriptase inhibitors (NNRTIs), and poor treatment outcomes on NNRTI-based FL antiretroviral therapy (ART) have been widely reported among infants and young children. There is a paucity of recent data on the use of protease inhibitor (PI)-based FL and SL regimens in children, but studies have reported poor tolerability, adherence problems and the development of PI resistance. Limited access to virological monitoring and HIV drug resistance testing contributes to delays in identifying treatment failure due to ADR and delays in switching to SL regimens in children. Implementation of FL ART regimens that have a higher barrier to developing resistance and are safe and well tolerated is required in order to attain global treatment targets. Although PI-based regimens may be effective as FL or SL treatment in children, lack of appropriate formulations leading to poor tolerability, drug-drug interactions, and cost considerations have negatively impacted their use among children in LMICs. There is hope that dolutegravir-based regimens recommended for children by the World Health Organization will be widely implemented once child-friendly formulations are available, and dosing and safety studies currently underway are completed, and that this will significantly improve treatment outcomes.
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