Testing genotypic and phenotypic resistance in human immunodeficiency virus type 1 isolates of clade B and other clades from children failing antiretroviral therapy

J Clin Microbiol. 2002 Dec;40(12):4512-9. doi: 10.1128/JCM.40.12.4512-4519.2002.

Abstract

The emergence of resistance to antiretroviral drugs is a major obstacle to the successful treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients. In this work, we correlate clinical and virological trends such as viral load (VL) and CD4 counts to genotypic and phenotypic antiretroviral (ARV) resistance profiles of HIV-1 isolates from the B and non-B subtypes found in vertically infected children failing ARV therapy. Plasma samples were collected from 52 vertically HIV-1-infected children failing different ARV therapies. Samples underwent HIV-1 pol sequencing and phenotyping and were clustered into subtypes by phylogenetic analysis. Clinical data from each patient were analyzed together with the resistance (genotypic and phenotypic) data obtained. Thirty-five samples were from subtype B, 10 samples were non-B (subtypes A, C, and F), and 7 were mosaic samples. There was no significant difference concerning treatment data between B and non-B clades. Prevalence of known drug resistance mutations revealed slightly significant differences among B and non-B subtypes: L10I, 21 and 64%, K20R, 13 and 43%, M36I, 34 and 100%, L63P, 76 and 36%, A71V/T, 24 and 0%, and V77I, 32 and 0%, respectively, in the protease (0.0001 </= P </= 0.0886), and D67N, 38 and 8%, K70R, 33 and 0%, R211K, 49 and 85%, and K219Q/E, 31 and 0%, respectively, in the reverse transcriptase (0.0256 </= P </= 0.0704). Significant differences were found only in secondary resistance mutations and did not reflect significant phenotypic variation between clade B and non-B.

MeSH terms

  • Adolescent
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Resistance, Viral*
  • Drug Therapy, Combination
  • Female
  • Genes, pol
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease / genetics
  • HIV Protease Inhibitors / pharmacology
  • HIV Protease Inhibitors / therapeutic use*
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / classification*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Male
  • Microbial Sensitivity Tests / methods
  • Mutation
  • Phenotype
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Treatment Failure

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • HIV Protease