title: Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children.
abstract: BACKGROUND
  Without virologic testing, HIV-infected African children starting antiretroviral (ARV) therapy are at risk for undetected virologic failure and the development of ARV resistance. We sought to determine the prevalence of early virologic failure (EVF), to characterize the evolution of ARV-resistance mutations and to predict the impact on second-line therapy.
  
  
  METHODS
  The prevalence of EVF (HIV RNA >400 copies/mL on sequential visits after 6 months of therapy) was identified among 120 HIV-infected Ugandan children starting ARV therapy. ARV mutations were identified by population sequencing of HIV-1 pol in sequential archived specimens. Composite discrete genotypic susceptibility scores were determined for second-line ARV regimens.
  
  
  RESULTS
  EVF occurred in 16 children (13%) and persisted throughout a median (interquartile ratio) 938 (760-1066) days of follow-up. M184V and nonnucleoside reverse transcriptase inhibitor-associated mutations emerged within 6 months of EVF; thymidine-analog-mutations arose after 12 months. Worse discrete genotypic susceptibility scores correlated with increasing duration of failure (Spearman R = -0.47; P = 0.001). Only 1 child met World Health Organization CD4 criteria for ARV failure at the time of EVF or during the follow-up period.
  
  
  CONCLUSIONS
  A significant portion of HIV-infected African children experience EVF that would be undetected using CD4/clinical monitoring and resulted in the accumulation of ARV mutations that could compromise second-line therapy options.
authors.affiliation: Department of Pediatrics, School of Medicine, University of California, San Francisco, San Francisco, CA 94143-0136, USA. ruelt@peds.ucsf.edu
authors.forename: Theodore D
authors.initials: TD
authors.lastname: Ruel
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Pelin
authors.initials: P
authors.lastname: Li
authors.forename: William
authors.initials: W
authors.lastname: Pasutti
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Charlebois
authors.forename: Teri
authors.initials: T
authors.lastname: Liegler
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Diane V
authors.initials: DV
authors.lastname: Havlir
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wong
authors.forename: Jane
authors.initials: J
authors.lastname: Achan
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D015995:Prevalence; D013997:Time Factors; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load / Q000187:drug effects; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D054302:pol Gene Products, Human Immunodeficiency Virus