Prevalence of minor variants of HIV strains at reverse transcriptase position 103 in therapy-naïve patients and their impact on the virological failure

J Clin Virol. 2009 May;45(1):34-8. doi: 10.1016/j.jcv.2009.03.002. Epub 2009 Apr 17.

Abstract

Background and objectives: Minority HIV-1 populations with resistance mutations might result in therapy failure. The prevalence of transmitted minorities in therapy-naïve patients and their influence on the virological outcome of the first-line-therapy need clarification.

Study design: The HIV reverse transcriptase (RT) of 159 therapy-naïve patients from the RESINA-cohort was genotyped. The relative amount of RT-K103N was measured by primer specific PCR. The response to first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-therapy was evaluated.

Results: Bulk-sequencing detected 1 NNRTI mutation (no K103N) in six patients (1.26%). K103N minorities were found in 20.1% of the samples, more frequently in HIV-1 non-B subtypes (40.6%) than in subtype B (15.0%) (p=0.0025). NNRTI treatment failed after 12 weeks in 24% of 17 patients with minority, but only in 15% of 67 patients without minority.

Conclusions: K103N minorities were found in 20.1% of the patients, whereas the prevalence of major K103N populations was 3% in the total RESINA-cohort. K103N minorities were more frequent in non-B subtypes. There is some evidence for a higher risk of NNRTI-treatment failure in patients with K103N minorities; however, the majority of patients with minority underwent a successful first-line-treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Cohort Studies
  • Data Interpretation, Statistical
  • Female
  • Genes, pol
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology
  • HIV Infections / virology*
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Prevalence
  • RNA, Viral / analysis
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Treatment Failure

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase