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- Title
Human Immunodeficiency Virus Type 1 Persistence Following Systemic Chemotherapy for Malignancy.
- Authors
Henrich, Timothy J.; Hobbs, Kristen S.; Hanhauser, Emily; Scully, Eileen; Hogan, Louise E.; Robles, Yvonne P.; Leadabrand, Kaitlyn S.; Marty, Francisco M.; Palmer, Christine D.; Jost, Stephanie; Körner, Christian; Li, Jonathan Z.; Gandhi, Rajesh T.; Hamdan, Ayad; Abramson, Jeremy; LaCasce, Ann S.; Kuritzkes, Daniel R.
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Expansion of HIV-infected CMV/EBV-specific CD4 + T cells may contribute to maintenance of the HIV DNA reservoir following chemotherapy.
- Subjects
CANCER chemotherapy; IMMUNODEFICIENCY; T cells; HIV infections; STEM cell transplantation; CYTOMEGALOVIRUS diseases; CYTOMEGALOVIRUSES
- Publication
Journal of Infectious Diseases, 2017, Vol 216, Issue 2, p254
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jix265