Characterization of HIV-1 Near Full-Length Proviral Genome Quasispecies from Patients with Undetectable Viral Load Undergoing First-Line HAART Therapy

Viruses. 2017 Dec 19;9(12):392. doi: 10.3390/v9120392.

Abstract

Increased access to highly active antiretroviral therapy (HAART) by human immunodeficiency virus postive (HIV⁺) individuals has become a reality worldwide. In Brazil, HAART currently reaches over half of HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. In this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV⁺ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG) assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23). Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.

Keywords: HAART; HIV-1; drug resistance; minority resistance mutations; quasispecies; undetectable viral load.

MeSH terms

  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active*
  • Brazil
  • Genome, Viral
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / classification*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Humans
  • Proviruses / classification*
  • Proviruses / genetics
  • Proviruses / isolation & purification
  • Quasispecies*
  • Sequence Analysis, DNA
  • Viral Load
  • Whole Genome Sequencing

Substances

  • Anti-Retroviral Agents