title: HIV Drug Resistance Among Children Initiating First-Line Antiretroviral Treatment in Uganda.
abstract: There are limited data on primary human immunodeficiency virus drug resistance (HIVDR) in pediatric populations. This study aimed to assess the prevalence of primary HIVDR and associated risk factors among children initiating first-line antiretroviral therapy (ART) in Uganda.
  
  
  
  At three Ugandan clinics, children (age <12 years) requiring ART were recruited between January 2010 and August 2011. Before starting ART, blood was collected for viral load and pol gene sequencing. Drug resistance mutations were determined using the 2010 International AIDS Society-USA mutation list. Risk factors for HIVDR were assessed with multivariate regression analysis.
  
  
  
  Three hundred nineteen HIV-infected children with a median age of 4.9 years were enrolled. Sequencing was successful in 279 children (87.5%). HIVDR was present in 10% of all children and 15.2% of children <3 years. Nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTI (NNRTI), and dual-class resistance was present in 5.7%, 7.5%, and 3.2%, respectively. HIVDR occurred in 35.7% of prevention of mother-to-child transmission (PMTCT)-exposed children, 15.6% in children with unknown PMTCT history, and 7.7% among antiretroviral-naive children. History of PMTCT exposure [adjusted odds ratio (AOR): 2.6, 95% CI: 1.3-5.1] or unknown PMTCT status (AOR: 3.8, 95% CI: 1.1-13.5), low CD4 (AOR: 2.2, 95% CI: 1.3-3.6), current breastfeeding (AOR: 7.4, 95% CI: 2.6-21), and current maternal ART use (AOR: 6.4, 95% CI: 3.4-11.9) emerged as risk factors for primary HIVDR in multivariate analysis.
  
  
  
  Pretreatment HIVDR is high, especially in children with PMTCT exposure. Protease inhibitor (PI)-based regimens are advocated by the World Health Organization, but availability in children is limited. Children with (unknown) PMTCT exposure, low CD4 count, current breastfeeding, or maternal ART need to be prioritized to receive PI-based regimens.
authors.affiliation: 1 Joint Clinical Research Centre (JCRC) , Kampala, Uganda .
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.affiliation: 2 Amsterdam Institute for Global Health and Development , Amsterdam, the Netherlands .|3 Department of Global Health, Academic Medical Center of the University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Kim Catherina Eve
authors.initials: KC
authors.lastname: Sigaloff
authors.affiliation: 2 Amsterdam Institute for Global Health and Development , Amsterdam, the Netherlands .|3 Department of Global Health, Academic Medical Center of the University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Tamara
authors.initials: T
authors.lastname: Sonia Boender
authors.affiliation: 1 Joint Clinical Research Centre (JCRC) , Kampala, Uganda .
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kaudha
authors.affiliation: 1 Joint Clinical Research Centre (JCRC) , Kampala, Uganda .
authors.forename: Joshua
authors.initials: J
authors.lastname: Kayiwa
authors.affiliation: 1 Joint Clinical Research Centre (JCRC) , Kampala, Uganda .
authors.forename: Victor
authors.initials: V
authors.lastname: Musiime
authors.affiliation: 1 Joint Clinical Research Centre (JCRC) , Kampala, Uganda .
authors.forename: Andrew
authors.initials: A
authors.lastname: Mukuye
authors.affiliation: 1 Joint Clinical Research Centre (JCRC) , Kampala, Uganda .
authors.forename: Mary
authors.initials: M
authors.lastname: Kiconco
authors.affiliation: 1 Joint Clinical Research Centre (JCRC) , Kampala, Uganda .
authors.forename: Immaculate
authors.initials: I
authors.lastname: Nankya
authors.affiliation: 1 Joint Clinical Research Centre (JCRC) , Kampala, Uganda .
authors.forename: Llilian
authors.initials: L
authors.lastname: Nakatudde-Katumba
authors.affiliation: 3 Department of Global Health, Academic Medical Center of the University of Amsterdam , Amsterdam, the Netherlands .|4 Emma Children's Hospital , Academic Medical Centre, Amsterdam, the Netherlands .
authors.forename: Job C J
authors.initials: JC
authors.lastname: Calis
authors.affiliation: 2 Amsterdam Institute for Global Health and Development , Amsterdam, the Netherlands .|3 Department of Global Health, Academic Medical Center of the University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Tobias F
authors.initials: TF
authors.lastname: Rinke de Wit
authors.affiliation: 1 Joint Clinical Research Centre (JCRC) , Kampala, Uganda .
authors.forename: Peter N
authors.initials: PN
authors.lastname: Mugyenyi
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D030541:Databases, Genetic; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000302:isolation & purification*; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D044966:Anti-Retroviral Agents; D054302:pol Gene Products, Human Immunodeficiency Virus