title: Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy.
abstract: BACKGROUND
  Antiretroviral therapy is provided by the Brazilian Ministry of Health to eligible HIV-infected individuals. Based on clinical and immunological classification, the Brazilian guidelines recommend dual or triple therapy for children. However, the development of drug-resistant strains or poor adherence to therapy could impact the efficacy of this approach.
  
  
  OBJECTIVE
  We examined relationships between RNA levels, CD4+ T-cell counts, treatment history, and the prevalence of drug-resistant variants in a cohort of HIV-1-infected children in Rio de Janeiro, Brazil.
  
  
  METHODS
  Direct sequencing of reverse transcriptase and protease genes from plasma was performed. Virologic and CD4+ T-cell counts responses to therapy were assessed by changes in HIV-1 RNA levels and CD4+ T-cell counts from baseline.
  
  
  RESULTS
  Thirty-seven patients were receiving dual therapy and 38 were on triple therapy at enrollment, segregated by antiretroviral history. Both groups had a higher increase in CD4+ T cell counts and a lower viral load in pre-treatment antiretroviral-naïve subjects. Notably, there was a direct correlation between the higher frequencies of drug-resistance mutations and cross-resistance with previous usage of antiretroviral (ARV) therapy in both groups. Non-B subtypes isolates were found in 21.3% of samples. A smaller increase in CD4+ T cell counts was found between non-B subtypes when compared to B-subtypes.
  
  
  CONCLUSIONS
  These results suggest that less immunological recovery and a higher number of mutations related to drug resistance were associated with previous usage of ARV and consequent higher time under drug selective pressure in these HIV-infected Brazilian children. These facts suggest the preferential use of triple drug combination as first line regimen in children.
authors.affiliation: Serviço de Doenças Infecciosas e Parasitárias, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil. emachado@biologia.ufrj.br
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Machado
authors.forename: John S
authors.initials: JS
authors.lastname: Lambert
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Watson
authors.forename: Adriana O
authors.initials: AO
authors.lastname: Afonso
authors.forename: Silvia M
authors.initials: SM
authors.lastname: da Cunha
authors.forename: Susie A
authors.initials: SA
authors.lastname: Nogueira
authors.forename: Elena
authors.initials: E
authors.lastname: Caride
authors.forename: Ricardo H
authors.initials: RH
authors.lastname: Oliveira
authors.forename: Anne M
authors.initials: AM
authors.lastname: Sill
authors.forename: Anthony
authors.initials: A
authors.lastname: DeVico
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001938:Brazil; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D019562:Viral Load; D014766:Viremia
chemical_list: D019380:Anti-HIV Agents; D018076:DNA, Complementary; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease