HIV sequence diversity during the early phase of infection is associated with HIV DNA reductions during antiretroviral therapy

J Med Virol. 2017 Jun;89(6):982-988. doi: 10.1002/jmv.24723. Epub 2017 Feb 27.

Abstract

The association between baseline human immunodeficiency virus (HIV) sequence diversity and HIV DNA decay after the initiation of antiretroviral therapy (ART) remains uncharacterized during the early stages of HIV infection. Samples were obtained from a cohort of 17 patients with early HIV infection (<6 months after infection) who initiated ART, and the C2V5 region of the HIV-1 envelope (env) gene was amplified via single genome amplification (SGA) to determine the peripheral plasma HIV quasispecies. We categorized HIV quasispecies into two groups according to baseline viral sequence genetic distance, which was determined by the Poisson-Fitter tool. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), viral load, and T cell subsets were measured prior to and after the initiation of ART. The median SGA sequence number was 17 (range 6-28). At baseline, we identified 7 patients with homogeneous viral populations (designated the Homogeneous group) and 10 patients with heterogeneous viral populations (designated the Heterogeneous group) based on SGA sequences. Both groups exhibited similar HIV DNA decay rates during the first 6 months of ART (P > 0.99), but the Homogenous group experienced more prominent decay than the Heterogeneous group after 6 months (P = 0.037). The Heterogeneous group had higher CD4 cell counts after ART initiation; however, both groups had comparable recovery in terms of CD4/CD8 ratios and CD8 T cell activation levels. Viral population homogeneity upon the initiation of ART is associated with a decrease in HIV DNA levels during ART. J. Med. Virol. 89:982-988, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: HIV DNA; HIV reservoir; early HIV infection; sequence diversity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • CD4-CD8 Ratio
  • Cluster Analysis
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Genetic Variation*
  • HIV / classification*
  • HIV / genetics*
  • HIV / isolation & purification
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Phylogeny
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Viral Load
  • Young Adult
  • env Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • Anti-Retroviral Agents
  • env Gene Products, Human Immunodeficiency Virus