HIV-1 evolution in patients undergoing immunotherapy with Tat, Rev, and Nef expressing dendritic cells followed by treatment interruption

AIDS. 2013 Nov 13;27(17):2679-89. doi: 10.1097/01.aids.0000433813.67662.92.

Abstract

Objectives: This study aimed to evaluate HIV sequence evolution in whole genes and in CD8 T-cell epitope regions following immunotherapy and subsequent analytical treatment interruption (ATI). A second objective of this study was to analyze associations between vaccine-specific immune responses and epitope mutation rates.

Design: HIV-1-infected patients on combined antiretroviral therapy (cART) were subjected to immunotherapy by the administration of an autologous dendritic cell-based therapeutic vaccine expressing Tat, Rev, and Nef and subsequent ATI.

Methods: HIV-1 genes were amplified and sequenced from plasma RNA obtained before initiation of cART as well as during ATI. Control sequences for virus evolution in untreated HIV-1-infected individuals were obtained from the HIV Sequence Database (Los Alamos). CD8 T-cell epitope regions were defined based on literature data and prediction models. HIV-1-specific immune responses were evaluated to analyze their impact on sequence evolution.

Results: Viral sequence evolution in the tat, rev, and nef genes of vaccinated patients was similar to that of controls. The number of mutations observed inside and outside CD8 T-cell epitopes was comparable for vaccine-targeted and nontargeted proteins. We found no evidence for an impact of vaccine-induced or enhanced immune responses on the number of mutations inside or outside epitopes.

Conclusion: Therapeutic vaccination of HIV-1-infected patients with a dendritic cell-based vaccine targeting Tat, Rev, and Nef did not affect virus evolution at the whole gene level nor at the CD8 T-cell epitope level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Retroviral Agents / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • Epitopes, T-Lymphocyte / genetics
  • Evolution, Molecular
  • HIV Infections / therapy*
  • HIV Infections / virology
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • Immunotherapy / methods*
  • RNA, Viral / blood
  • RNA, Viral / genetics
  • Sequence Analysis, DNA
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / immunology*
  • rev Gene Products, Human Immunodeficiency Virus / genetics
  • rev Gene Products, Human Immunodeficiency Virus / immunology*
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • Anti-Retroviral Agents
  • Epitopes, T-Lymphocyte
  • RNA, Viral
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • rev Gene Products, Human Immunodeficiency Virus
  • rev protein, Human Immunodeficiency Virus-1
  • tat Gene Products, Human Immunodeficiency Virus