Minority drug-resistant HIV-1 variants in treatment naïve East-African and Caucasian patients detected by allele-specific real-time PCR

PLoS One. 2014 Oct 21;9(10):e111042. doi: 10.1371/journal.pone.0111042. eCollection 2014.

Abstract

Objective: To assess the presence of two major non-nucleoside reverse transcriptase inhibitors (NNRTI) drug resistance mutations (DRMs), Y181C and K103N, in minor viral quasispecies of treatment naïve HIV-1 infected East-African and Swedish patients by allele-specific polymerase chain reaction (AS-PCR).

Methods: Treatment naïve adults (n=191) with three epidemiological backgrounds were included: 92 Ethiopians living in Ethiopia; 55 East-Africans who had migrated to Sweden; and 44 Caucasians living in Sweden. The pol gene was analysed by standard population sequencing and by AS-PCR for the detection of Y181C and K103N.

Results: The Y181C was detected in the minority quasispecies of six Ethiopians (6.5%), in two Caucasians (4.5%), and in one East-African (1.8%). The K103N was detected in one East- African (1.8%), by both methods. The proportion of mutants ranged from 0.25% to 17.5%. Additional DRMs were found in all three treatment naïve patient groups by population sequencing.

Conclusions: Major NNRTI mutations can be found by AS-PCR in minor quasispecies of treatment naïve HIV-1 infected Ethiopians living in Ethiopia, in East-African and Caucasian patients living in Sweden in whom population sequencing reveal wild-type virus only. Surveys with standard sequencing are likely to underestimate transmitted drug resistance and the presence of resistant minor quasispecies in treatment naïve patients should be topic for future large scale studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Drug Resistance, Viral / genetics*
  • Ethiopia
  • Female
  • Genes, pol / genetics*
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / pathology
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Male
  • Mutation
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Sweden

Substances

  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase

Grants and funding

This study was supported by the European and Developing Countries Clinical Trial Partnership, SIDA, the Swedish Civil Contingencies Agency, Swedish Research Council and 7th Framework Programme of European Union, Collaborative HIV and Anti-HIV Drug Resistance Network. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.