Genotypic resistance and HIV-1 subtype in Brazilian children on dual and triple combination therapy

J Clin Virol. 2004 May;30(1):24-31. doi: 10.1016/j.jcv.2003.08.001.

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.

Objectives: 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.

Study design: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Brasilien
  • CD4 Lymphocyte Count
  • Child
  • Child, Preschool
  • DNA, Complementary / chemistry
  • DNA, Complementary / isolation & purification
  • Drug Resistance, Viral / genetics*
  • Drug Therapy, Combination
  • Evolution, Molecular
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV Protease / genetics
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Mutation, Missense
  • RNA, Viral / blood
  • RNA, Viral / isolation & purification
  • Selection, Genetic
  • Sequence Analysis, DNA
  • Viral Load
  • Viremia

Substances

  • Anti-HIV Agents
  • DNA, Complementary
  • RNA, Viral
  • HIV Reverse Transcriptase
  • HIV Protease

Associated data

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