Human immunodeficiency virus type 1 persistence following systemic chemotherapy for malignancy

Timothy J. Henrich, Kristen S. Hobbs, Emily Hanhauser, Eileen Scully, Louise E. Hogan, Yvonne P. Robles, Kaitlyn S. Leadabrand, Francisco M. Marty, Christine D. Palmer, Stephanie Jost, Christian Körner, Jonathan Z. Li, Rajesh T. Gandhi, Ayad Hamdan, Jeremy Abramson, Ann S. LaCasce, Daniel R. Kuritzkes

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Systemic chemotherapies for various malignancies have been shown to significantly, yet transiently, decrease numbers of CD4+ T lymphocytes, a major reservoir for human immunodeficiency virus type 1 (HIV-1) infection. However, little is known about the impact of cytoreductive chemotherapy on HIV-1 reservoir dynamics, persistence, and immune responses. Methods. We investigated the changes in peripheral CD4+ T-cell-associated HIV-1 DNA and RNA levels, lymphocyte activation, viral population structure, and virus-specific immune responses in a longitudinal cohort of 15 HIV-1-infected individuals receiving systemic chemotherapy or subsequent autologous stem cell transplantation for treatment of hematological malignancies and solid tumors. Results. Despite a transient reduction in CD4+ T cells capable of harboring HIV-1, a 1.7-and 3.3-fold increase in mean CD4+ T-cell-associated HIV-1 RNA and DNA, respectively, were observed months following completion of chemotherapy in individuals on antiretroviral therapy. We also observed changes in CD4+ T-cell population diversity and clonal viral sequence expansion during CD4+ T-cell reconstitution following chemotherapy cessation. Finally, HIV-1 DNA was preferentially, and in some cases exclusively, detected in cytomegalovirus (CMV)-and Epstein-Barr virus (EBV)-responsive CD4+ T cells following chemotherapy. Conclusions. Expansion of HIV-infected CMV/EBV-specific CD4 + T cells may contribute to maintenance of the HIV DNA reservoir following chemotherapy.

Original languageEnglish (US)
Pages (from-to)254-262
Number of pages9
JournalJournal of Infectious Diseases
Volume216
Issue number2
DOIs
StatePublished - Jul 15 2017

Keywords

  • Chemotherapy
  • Cytomegalovirus infection
  • HIV-1
  • Lymphoma
  • Stem cell transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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