Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal

Of the 12 million people who inject drugs worldwide, 13% live with HIV. Whether opioid use impacts HIV pathogenesis and latency is an outstanding question. To gain insight into whether opioid use influences the proviral landscape and latent HIV reservoir, we performed intact proviral DNA assays (IPD...

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Main Authors: Binita Basukala, Sarah Rossi, Sally Bendiks, Natalia Gnatienko, Gregory Patts, Evgeny Krupitsky, Dmitry Lioznov, Kaku So-Armah, Manish Sagar, Christine Cheng, Andrew J. Henderson
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/2/415
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author Binita Basukala
Sarah Rossi
Sally Bendiks
Natalia Gnatienko
Gregory Patts
Evgeny Krupitsky
Dmitry Lioznov
Kaku So-Armah
Manish Sagar
Christine Cheng
Andrew J. Henderson
author_facet Binita Basukala
Sarah Rossi
Sally Bendiks
Natalia Gnatienko
Gregory Patts
Evgeny Krupitsky
Dmitry Lioznov
Kaku So-Armah
Manish Sagar
Christine Cheng
Andrew J. Henderson
author_sort Binita Basukala
collection DOAJ
description Of the 12 million people who inject drugs worldwide, 13% live with HIV. Whether opioid use impacts HIV pathogenesis and latency is an outstanding question. To gain insight into whether opioid use influences the proviral landscape and latent HIV reservoir, we performed intact proviral DNA assays (IPDA) on peripheral blood mononuclear cells (PBMCs) from antiretroviral therapy (ART)-suppressed people living with HIV (PWH) with or without current opioid use. No differences were observed between PWH with and without opioid use in the frequency of HIV intact and defective proviral genomes. To evaluate the latent reservoir, we activated PBMCs from ART-suppressed PWH with or without opioid use and assessed the induction of HIV RNA. PWH using opioids had diminished responses to ex vivo HIV reactivation, suggesting a smaller reversible reservoir of HIV-1 latently infected cells. However, in vitro studies using primary CD4+ T cells treated with morphine showed no effect of opioids on HIV-1 infection, replication or latency establishment. The discrepancy in our results from in vitro and clinical samples suggests that while opioids may not directly impact HIV replication, latency and reactivation in CD4+ T cells, opioid use may indirectly shape the HIV reservoir in vivo by modulating general immune functions.
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spelling doaj.art-71e4143ec84f4c95b40e8853fb0b58af2023-11-16T23:48:43ZengMDPI AGViruses1999-49152023-02-0115241510.3390/v15020415Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency ReversalBinita Basukala0Sarah Rossi1Sally Bendiks2Natalia Gnatienko3Gregory Patts4Evgeny Krupitsky5Dmitry Lioznov6Kaku So-Armah7Manish Sagar8Christine Cheng9Andrew J. Henderson10Department of Biology, Boston University, Boston, MA 02215, USAClinical Addiction Research and Education (CARE) Unit, Department of Medicine, Section of General Internal Medicine, Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USAClinical Addiction Research and Education (CARE) Unit, Department of Medicine, Section of General Internal Medicine, Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USAClinical Addiction Research and Education (CARE) Unit, Department of Medicine, Section of General Internal Medicine, Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USABiostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, MA 02118, USALaboratory of Clinical Pharmacology of Addictions, Pavlov First St. Petersburg State Medical University, Saint-Petersburg 197022, RussiaLaboratory of Clinical Pharmacology of Addictions, Pavlov First St. Petersburg State Medical University, Saint-Petersburg 197022, RussiaClinical Addiction Research and Education (CARE) Unit, Department of Medicine, Section of General Internal Medicine, Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USADepartment of Medicine, Section of Infectious Diseases, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USADepartment of Biology, Boston University, Boston, MA 02215, USADepartment of Medicine, Section of Infectious Diseases, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USAOf the 12 million people who inject drugs worldwide, 13% live with HIV. Whether opioid use impacts HIV pathogenesis and latency is an outstanding question. To gain insight into whether opioid use influences the proviral landscape and latent HIV reservoir, we performed intact proviral DNA assays (IPDA) on peripheral blood mononuclear cells (PBMCs) from antiretroviral therapy (ART)-suppressed people living with HIV (PWH) with or without current opioid use. No differences were observed between PWH with and without opioid use in the frequency of HIV intact and defective proviral genomes. To evaluate the latent reservoir, we activated PBMCs from ART-suppressed PWH with or without opioid use and assessed the induction of HIV RNA. PWH using opioids had diminished responses to ex vivo HIV reactivation, suggesting a smaller reversible reservoir of HIV-1 latently infected cells. However, in vitro studies using primary CD4+ T cells treated with morphine showed no effect of opioids on HIV-1 infection, replication or latency establishment. The discrepancy in our results from in vitro and clinical samples suggests that while opioids may not directly impact HIV replication, latency and reactivation in CD4+ T cells, opioid use may indirectly shape the HIV reservoir in vivo by modulating general immune functions.https://www.mdpi.com/1999-4915/15/2/415opioid useHIV pathogenesisHIV latency
spellingShingle Binita Basukala
Sarah Rossi
Sally Bendiks
Natalia Gnatienko
Gregory Patts
Evgeny Krupitsky
Dmitry Lioznov
Kaku So-Armah
Manish Sagar
Christine Cheng
Andrew J. Henderson
Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal
Viruses
opioid use
HIV pathogenesis
HIV latency
title Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal
title_full Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal
title_fullStr Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal
title_full_unstemmed Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal
title_short Virally Suppressed People Living with HIV Who Use Opioids Have Diminished Latency Reversal
title_sort virally suppressed people living with hiv who use opioids have diminished latency reversal
topic opioid use
HIV pathogenesis
HIV latency
url https://www.mdpi.com/1999-4915/15/2/415
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