M H W Huibers1,2, P Moons1,3, M Cornelissen4, F Zorgdrager4, N Maseko3, M B Gushu3, O H Iwajomo5,6, M Boele van Hensbroek1,2, J C J Calis1,7. 1. Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. 2. Amsterdam Institute of Global Health Development (AIGHD), Amsterdam, The Netherlands. 3. Department of Paediatrics, University of Malawi College of Medicine, Blantyre, Malawi. 4. Laboratory of Experimental Virology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. 5. School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK. 6. Malawi Liverpool Wellcome Trust Clinical Research Program, University of Malawi College of Medicine, Blantyre, Malawi. 7. Department of Paediatric Intensive Care, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Abstract
Background: Drug resistance mutations (DRMs) increasingly jeopardize paediatric HIV programmes in sub-Saharan Africa. As individual monitoring of DRMs and viral loads has limited availability, population data on DRMs are essential to determine first-line susceptibility. Paediatric data from sub-Saharan Africa are scarce and unavailable for Malawi. Objectives: To determine the prevalence of virological failure (VF) and DRMs among ART-naive HIV-infected Malawian children during the first year of first-line ART. Methods: In a prospective cohort of HIV-infected Malawian children, on first-line treatment, children were followed monthly; blood was collected for viral load testing (6 and 12 months) and genotypic resistance testing (12 months). VF was defined as at least one viral load >1000 copies/mL or death after 6 months of ART. DRMs were identified and susceptibility to NRTIs and NNRTIs was scored using the Stanford algorithm and by calculating genotypic susceptibility scores (GSSs). Results: VF occurred in 66% (23/35) of the children during 12 months of follow-up. DRMs were detected in 44% (15/34); all had NNRTI resistance and 12% (4/34) had dual-class NNRTI/NRTI resistance. Reduced susceptibility (DRMs and GSS <3) was seen in 41% (14/34) to their current first-line regimen. High-level resistance was most common for nevirapine [26% (9/34)]. Conclusions: In this first report on VF and DRMs in children on first-line ART in Malawi, the rates of VF and DRMs were alarmingly high. Paediatric HIV programmes in sub-Saharan Africa should emphasize programmatic evaluation of VF and include detection of DRMs to adjust and design adequate first- and second-line regimens and prevent widespread resistance in children.
Background: Drug resistance mutations (DRMs) increasingly jeopardize paediatric HIV programmes in sub-Saharan Africa. As individual monitoring of DRMs and viral loads has limited availability, population data on DRMs are essential to determine first-line susceptibility. Paediatric data from sub-Saharan Africa are scarce and unavailable for Malawi. Objectives: To determine the prevalence of virological failure (VF) and DRMs among ART-naive HIV-infected Malawianchildren during the first year of first-line ART. Methods: In a prospective cohort of HIV-infected Malawianchildren, on first-line treatment, children were followed monthly; blood was collected for viral load testing (6 and 12 months) and genotypic resistance testing (12 months). VF was defined as at least one viral load >1000 copies/mL or death after 6 months of ART. DRMs were identified and susceptibility to NRTIs and NNRTIs was scored using the Stanford algorithm and by calculating genotypic susceptibility scores (GSSs). Results:VF occurred in 66% (23/35) of the children during 12 months of follow-up. DRMs were detected in 44% (15/34); all had NNRTI resistance and 12% (4/34) had dual-class NNRTI/NRTI resistance. Reduced susceptibility (DRMs and GSS <3) was seen in 41% (14/34) to their current first-line regimen. High-level resistance was most common for nevirapine [26% (9/34)]. Conclusions: In this first report on VF and DRMs in children on first-line ART in Malawi, the rates of VF and DRMs were alarmingly high. Paediatric HIV programmes in sub-Saharan Africa should emphasize programmatic evaluation of VF and include detection of DRMs to adjust and design adequate first- and second-line regimens and prevent widespread resistance in children.
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