title: Alarming increase in pretreatment HIV drug resistance in children living in sub-Saharan Africa: a systematic review and meta-analysis.
abstract: Children have an augmented risk of pretreatment HIV drug resistance (PDR) due to exposure to antiretroviral drugs for the prevention of mother-to-child transmission (PMTCT). Paediatric data are essential to evaluate the effectiveness of the restricted number of paediatric regimens currently available, but these data are scarce.
  
  
  
  We conducted a systematic review of the literature on PDR in children (median age ≤12 years) in sub-Saharan Africa. We separately extracted the proportion of children with PDR for children with and without prior PMTCT exposure, used random-effects meta-analysis to pool proportions and used meta-regression to assess subgroup differences.
  
  
  
  We included 19 studies representing 2617 children from 13 countries. The pooled PDR prevalence was 42.7% (95% CI 26.2%-59.1%) among PMTCT-exposed children and 12.7% (95% CI 6.7%-18.7%) among PMTCT-unexposed children (P = 0.004). The PDR prevalence in PMTCT-unexposed children increased from 0% in 2004 to 26.8% in 2013 (P = 0.009). NNRTI mutations were detected in 32.4% (95% CI 18.7%-46.1%) of PMTCT-exposed children and in 9.7% (95% CI 4.6%-14.8%) of PMTCT-unexposed children; PI mutations were uncommon (<2.5%). PDR was more common in children aged <3 years compared with children aged ≥3 years [40.9% (95% CI 27.6%-54.3%) versus 17.6% (95% CI 8.9%-26.3%), respectively (P = 0.025)].
  
  
  
  The PDR prevalence in African children is high and rapidly increasing. Even in PMTCT-unexposed children, the most recent reports indicate that PDR is present in up to a third of children starting first-line therapy. Our data underscore the importance of initiating PI-based first-line ART in young children (<3 years of age) and suggest that older children may also benefit from this approach.
authors.affiliation: Amsterdam Institute for Global Health and Development & Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands r.boerma@aighd.org.|Global Child Health Group, Emma Children's Hospital, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: R S
authors.initials: RS
authors.lastname: Boerma
authors.affiliation: Amsterdam Institute for Global Health and Development & Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.|Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: K C E
authors.initials: KC
authors.lastname: Sigaloff
authors.affiliation: Department of Haematology, University Teaching Hospital, University of Lagos, Lagos, Nigeria.
authors.forename: A S
authors.initials: AS
authors.lastname: Akanmu
authors.affiliation: Amsterdam Institute for Global Health and Development & Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Inzaule
authors.affiliation: Global Child Health Group, Emma Children's Hospital, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Boele van Hensbroek
authors.affiliation: Amsterdam Institute for Global Health and Development & Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: T F
authors.initials: TF
authors.lastname: Rinke de Wit
authors.affiliation: Global Child Health Group, Emma Children's Hospital, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.|Department of Pediatric Intensive Care, Emma Children's Hospital, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Calis
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015995:Prevalence