Human Immunodeficiency Virus Type 1 Persistence Following Systemic Chemotherapy for Malignancy - PubMed (original) (raw)
. 2017 Jul 15;216(2):254-262.
doi: 10.1093/infdis/jix265.
Timothy J Henrich 1 2 3, Emily Hanhauser 1 2, Eileen Scully 2 3 4, Louise E Hogan 1 2 3, Yvonne P Robles 2, Kaitlyn S Leadabrand 1, Francisco M Marty 2 3 4, Christine D Palmer 5, Stephanie Jost 5 6, Christian Körner 5, Jonathan Z Li 2 3, Rajesh T Gandhi 3 5 7, Ayad Hamdan 3 6, Jeremy Abramson 3 7, Ann S LaCasce 3 4, Daniel R Kuritzkes 2 3
Affiliations
- PMID: 28838149
- PMCID: PMC5853412
- DOI: 10.1093/infdis/jix265
Human Immunodeficiency Virus Type 1 Persistence Following Systemic Chemotherapy for Malignancy
Timothy J Henrich et al. J Infect Dis. 2017.
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.
Keywords: HIV-1; chemotherapy; cytomegalovirus infection; lymphoma; stem cell transplantation.
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Figures
Figure 1.
CD4+ T cell–associated human immunodeficiency virus (HIV) DNA and RNA levels prior to and following completion of chemotherapy for hematologic malignancies and Kaposi sarcoma. Significant increases in both HIV DNA (A) and HIV RNA (C) in paired analyses were observed following completion of chemotherapy (postchemotherapy time points) compared with prechemotherapy or the first sampling time point while receiving cancer treatment (n = 10). Statistical significance was lost if only prechemotherapy time points are compared with those after completion of therapy for both DNA (B) and RNA (D), but paired sample size was smaller (n = 7), and up to a 1 log increase in DNA levels was still observed. Bars represent mean values and standard error. Paired, nonparametric Wilcoxon tests were used.
Figure 2.
Mean percentages of intracellular Ki67 expression and surface expression of CD38, HLA-DR, and CD57 on CD4+ and CD8+ T cells prior and following completion of chemotherapy in participants with lymphoma or Kaposi sarcoma. Nonsignificant decreases in T-cell activation (CD38+ HLA-DR+ dual positive) and proliferation (Ki67+) were observed by the second postchemotherapy sampling time point. Bars represent mean values and standard error.
Figure 3.
Maximum likelihood phylogenetic trees of single-genome human immunodeficiency virus type 1 (HIV-1) envelope DNA sequences from pre- or on-chemotherapy and postchemotherapy CD4+ T cells in patients with lymphoma on stable antiretroviral therapy throughout chemotherapy. Oligoclonal clustering of sequences was observed only following completion of chemotherapy in participants 4 and 6, with an increase in the number of near-identical envelope sequences following chemotherapy in participant 7. Phylogenetic trees were generated using bootstrapped, generalized time-reversible models. Bars represent genetic distance. Mean genetic distances for each participant time point are as follows: participant 2 prechemotherapy D = 0.019, postchemotherapy D = 0.032; participant 4 prechemotherapy D = 0.015, first postchemotherapy D = 0.032, second postchemotherapy D = 0.012; participant 6 prechemotherapy D = 0.018, postchemotherapy D = 0.019; participant 7 first on-chemotherapy D = 0.046, postchemotherapy D = 0.033. When excluding the single postchemotherapy outlier sequence from participant 6, the prechemotherapy D = 0.024 and postchemotherapy D = 0.013.
Figure 4.
Functional CD4+ T-cell responses to Epstein-Barr virus (EBV)/cytomegalovirus (CMV) lysate stimulation and CD4+ T cell–associated human immunodeficiency virus (HIV) DNA levels within responsive and unresponsive cells. CD4+ T cells were exposed to CMV/EBV lysates followed by fluorescence-activated cell sorting and enumeration of cells that produced interleukin 2 (IL-2) and/or interferon gamma (IFN-γ) (A). HIV DNA extracted and enumerated by quantitative polymerase chain reaction (qPCR) was found to be highest in cells responding to CMV/EBV antigen despite these cells being the least frequent (B).
Similar articles
- Asymptomatic CMV Replication During Early Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower CD4/CD8 Ratio During HIV Treatment.
Smith DM, Nakazawa M, Freeman ML, Anderson CM, Oliveira MF, Little SJ, Gianella S. Smith DM, et al. Clin Infect Dis. 2016 Dec 1;63(11):1517-1524. doi: 10.1093/cid/ciw612. Epub 2016 Sep 6. Clin Infect Dis. 2016. PMID: 27601222 Free PMC article. - Subclinical Cytomegalovirus DNA Is Associated with CD4 T Cell Activation and Impaired CD8 T Cell CD107a Expression in People Living with HIV despite Early Antiretroviral Therapy.
Christensen-Quick A, Massanella M, Frick A, Rawlings SA, Spina C, Vargas-Meneses M, Schrier R, Nakazawa M, Anderson C, Gianella S. Christensen-Quick A, et al. J Virol. 2019 Jun 14;93(13):e00179-19. doi: 10.1128/JVI.00179-19. Print 2019 Jul 1. J Virol. 2019. PMID: 31019052 Free PMC article. - Subclinical Cytomegalovirus and Epstein-Barr Virus Shedding Is Associated with Increasing HIV DNA Molecular Diversity in Peripheral Blood during Suppressive Antiretroviral Therapy.
Chaillon A, Nakazawa M, Rawlings SA, Curtin G, Caballero G, Scott B, Anderson C, Gianella S. Chaillon A, et al. J Virol. 2020 Sep 15;94(19):e00927-20. doi: 10.1128/JVI.00927-20. Print 2020 Sep 15. J Virol. 2020. PMID: 32641485 Free PMC article. - Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy.
Pierson T, McArthur J, Siliciano RF. Pierson T, et al. Annu Rev Immunol. 2000;18:665-708. doi: 10.1146/annurev.immunol.18.1.665. Annu Rev Immunol. 2000. PMID: 10837072 Review. - Cytomegalovirus and HIV Persistence: Pouring Gas on the Fire.
Christensen-Quick A, Vanpouille C, Lisco A, Gianella S. Christensen-Quick A, et al. AIDS Res Hum Retroviruses. 2017 Nov;33(S1):S23-S30. doi: 10.1089/aid.2017.0145. AIDS Res Hum Retroviruses. 2017. PMID: 29140108 Free PMC article. Review.
Cited by
- Atherosclerosis and Cardiovascular Complications in People Living with HIV: A Focused Review.
Paternò Raddusa MS, Marino A, Celesia BM, Spampinato S, Giarratana C, Venanzi Rullo E, Cacopardo B, Nunnari G. Paternò Raddusa MS, et al. Infect Dis Rep. 2024 Sep 1;16(5):846-863. doi: 10.3390/idr16050066. Infect Dis Rep. 2024. PMID: 39311207 Free PMC article. Review. - Spatial technologies to evaluate the HIV-1 reservoir and its microenvironment in the lymph node.
Zaman F, Smith ML, Balagopal A, Durand CM, Redd AD, Tobian AAR. Zaman F, et al. mBio. 2024 Aug 14;15(8):e0190924. doi: 10.1128/mbio.01909-24. Epub 2024 Jul 26. mBio. 2024. PMID: 39058091 Free PMC article. Review. - The latent reservoir of inducible, infectious HIV-1 does not decrease despite decades of antiretroviral therapy.
McMyn NF, Varriale J, Fray EJ, Zitzmann C, MacLeod H, Lai J, Singhal A, Moskovljevic M, Garcia MA, Lopez BM, Hariharan V, Rhodehouse K, Lynn K, Tebas P, Mounzer K, Montaner LJ, Benko E, Kovacs C, Hoh R, Simonetti FR, Laird GM, Deeks SG, Ribeiro RM, Perelson AS, Siliciano RF, Siliciano JM. McMyn NF, et al. J Clin Invest. 2023 Sep 1;133(17):e171554. doi: 10.1172/JCI171554. J Clin Invest. 2023. PMID: 37463049 Free PMC article. - Antigen specificities of HIV-infected cells: A role in infection and persistence?
Faua C, Fafi-Kremer S, Gantner P. Faua C, et al. J Virus Erad. 2023 Jun 1;9(2):100329. doi: 10.1016/j.jve.2023.100329. eCollection 2023 Jun. J Virus Erad. 2023. PMID: 37440870 Free PMC article. Review. - HIV-1 remission and possible cure in a woman after haplo-cord blood transplant.
Hsu J, Van Besien K, Glesby MJ, Pahwa S, Coletti A, Warshaw MG, Petz L, Moore TB, Chen YH, Pallikkuth S, Dhummakupt A, Cortado R, Golner A, Bone F, Baldo M, Riches M, Mellors JW, Tobin NH, Browning R, Persaud D, Bryson Y; International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1107 Team. Hsu J, et al. Cell. 2023 Mar 16;186(6):1115-1126.e8. doi: 10.1016/j.cell.2023.02.030. Cell. 2023. PMID: 36931242 Free PMC article.
References
- Siliciano JD, Kajdas J, Finzi D et al. . Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 2003; 9:727–8. - PubMed
- Chun TW, Justement JS, Moir S et al. . Decay of the HIV reservoir in patients receiving antiretroviral therapy for extended periods: implications for eradication of virus. J Infect Dis 2007; 195:1762–4. - PubMed
- Mackall CL, Fleisher TA, Brown MR et al. . Lymphocyte depletion during treatment with intensive chemotherapy for cancer. Blood 1994; 84:2221–8. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials