Claudia S Crowell1, Almoustapha I Maiga, Mariam Sylla, Babafemi Taiwo, Niaboula Kone, Assaf P Oron, Robert L Murphy, Anne-Geneviève Marcelin, Ban Traore, Djeneba B Fofana, Gilles Peytavin, Ellen G Chadwick. 1. From the *Department of Pediatrics, Division of Infectious Diseases, University of Washington, and †Seattle Children's Hospital, Seattle, Washington; ‡Unité d'Epidémiologie Moléculaire de la Résistance du VIH aux ARV, SEREFO, §University of Sciences, Techniques and Technologies of Bamako, and ¶Department of Pediatrics, University Hospital Gabriel Touré, Bamako, Mali; ‖Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois; **Seattle Children's Research Institute, Children's Core for Biomedical Statistics, Seattle, Washington; ††Department of Virology, Sorbonne Université, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique, ‡‡Department of Pharmaco-Toxicology, APHP, Bichat-Claude Bernard Hospital, and §§Paris Diderot University, Sorbonne Paris Cité, IAME, INSERM UMR 1137, Paris, France; and ¶¶Department of Pediatrics, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois.
Abstract
BACKGROUND: Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infected children <10 years of age initiating ART in Mali. METHODS: Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death >1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance. RESULTS: One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died >1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P < 0.001) and protease inhibitor-based ART initiation among children without baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use. CONCLUSIONS: Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.
BACKGROUND: Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infectedchildren in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infectedchildren <10 years of age initiating ART in Mali. METHODS: Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death >1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance. RESULTS: One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died >1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P < 0.001) and protease inhibitor-based ART initiation among children without baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use. CONCLUSIONS: Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.
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