Insights about minority HIV-1 strains in transmitted drug resistance mutation dynamics and disease progression

J Antimicrob Chemother. 2018 Jul 1;73(7):1930-1934. doi: 10.1093/jac/dky132.

Abstract

Objectives: The presence of minority transmitted drug resistance mutations was assessed using ultra-deep sequencing and correlated with disease progression among recently HIV-1-infected individuals from Brazil.

Methods: Samples at baseline during recent infection and 1 year after the establishment of the infection were analysed. Viral RNA and proviral DNA from 25 individuals were subjected to ultra-deep sequencing of the reverse transcriptase and protease regions of HIV-1.

Results: Viral strains carrying transmitted drug resistance mutations were detected in 9 out of the 25 patients, for all major antiretroviral classes, ranging from one to five mutations per patient. Ultra-deep sequencing detected strains with frequencies as low as 1.6% and only strains with frequencies >20% were detected by population plasma sequencing (three patients). Transmitted drug resistance strains with frequencies <14.8% did not persist upon established infection. The presence of transmitted drug resistance mutations was negatively correlated with the viral load and with CD4+ T cell count decay.

Conclusions: Transmitted drug resistance mutations representing small percentages of the viral population do not persist during infection because they are negatively selected in the first year after HIV-1 seroconversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Brazil
  • Cohort Studies
  • Disease Progression*
  • Drug Resistance, Viral / genetics*
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Seropositivity
  • HIV-1 / genetics*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation
  • Proviruses / genetics
  • RNA, Viral / genetics
  • Viral Load / drug effects*

Substances

  • Anti-HIV Agents
  • RNA, Viral