Human Immunodeficiency Virus Type 1 Persistence Following Systemic Chemotherapy for Malignancy.

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2017-07

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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.

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CD4-Positive T-Lymphocytes, Humans, Cytomegalovirus, Herpesvirus 4, Human, HIV-1, Cytomegalovirus Infections, HIV Infections, Neoplasms, DNA, Viral, RNA, Viral, Drug Therapy, Antiretroviral Therapy, Highly Active, Stem Cell Transplantation, Viral Load, Prospective Studies, Lymphocyte Activation, Virus Replication, Female, Male

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https://hdl.handle.net/10161/30019

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https://creativecommons.org/licenses/by-nc/4.0

Published Version (Please cite this version)

10.1093/infdis/jix265

Publication Info

Henrich, Timothy J, Kristen S Hobbs, Emily Hanhauser, Eileen Scully, Louise E Hogan, Yvonne P Robles, Kaitlyn S Leadabrand, Francisco M Marty, et al. (2017). Human Immunodeficiency Virus Type 1 Persistence Following Systemic Chemotherapy for Malignancy. The Journal of infectious diseases, 216(2). pp. 254–262. 10.1093/infdis/jix265 Retrieved from https://hdl.handle.net/10161/30019.

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Jost

Stephanie Rachel Jost

Associate Professor in Surgery

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